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| BabyScreen+ newborn screening v1.72 | KLHL3 |
Zornitza Stark gene: KLHL3 was added gene: KLHL3 was added to BabyScreen+ newborn screening. Sources: Expert list treatable, endocrine tags were added to gene: KLHL3. Mode of inheritance for gene: KLHL3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: KLHL3 were set to Pseudohypoaldosteronism, type IID, MIM# 614495 Review for gene: KLHL3 was set to GREEN Added comment: Established gene disease association. Results in hyperkalaemia and later, the development of hypertension. Treatment: thiazide diuretics normalise electrolytes Non-genetic confirmatory testing: electrolytes Sources: Expert list |
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| BabyScreen+ newborn screening v1.50 | CUL3 |
Zornitza Stark gene: CUL3 was added gene: CUL3 was added to BabyScreen+ newborn screening. Sources: Expert list treatable, endocrine tags were added to gene: CUL3. Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: CUL3 were set to Pseudohypoaldosteronism, type IIE 614496 Review for gene: CUL3 was set to GREEN Added comment: Established gene-disease association. Variants in this gene also cause a neurodevelopmental disorder; however, there is some genotype-phenotype correlation literature to help distinguish the two. Results in hyperkalaemia and development of hypertension. However, the onset of hypertension is generally later in life. Treatment: thiazide diuretics normalise biochemical abnormalities Sources: Expert list |
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| BabyScreen+ newborn screening v1.24 | ATRX | Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Intellectual disability-hypotonic facies syndrome, X-linked, MIM# 309580 to ATR-X-related syndrome MONDO:0016980 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.2141 | ABHD12 |
Lilian Downie gene: ABHD12 was added gene: ABHD12 was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: ABHD12 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ABHD12 were set to Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract MIM#612674 Review for gene: ABHD12 was set to RED Added comment: Age of onset not consistently under 5 for treatable elements such as hearing loss. Sources: Expert list |
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| BabyScreen+ newborn screening v0.2062 | SAR1B |
Zornitza Stark gene: SAR1B was added gene: SAR1B was added to Baby Screen+ newborn screening. Sources: Expert list treatable, gastrointestinal tags were added to gene: SAR1B. Mode of inheritance for gene: SAR1B was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SAR1B were set to Chylomicron retention disease, MIM# 246700 Review for gene: SAR1B was set to GREEN Added comment: Chylomicron retention disease is an autosomal recessive disorder of severe fat malabsorption associated with failure to thrive in infancy. Well established gene-disease association. Congenital onset. Treatment: low-fat diet with supplementation of fat-soluble vitamins (A, D, E, and K) and oral essential fatty acid supplementation Non-genetic confirmatory testing: total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol Sources: Expert list |
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| BabyScreen+ newborn screening v0.2052 | TMEM165 |
Lilian Downie gene: TMEM165 was added gene: TMEM165 was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: TMEM165 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM165 were set to PMID: 28323990, PMID: 35693943, PMID: 22683087 Phenotypes for gene: TMEM165 were set to Congenital disorder of glycosylation, type IIk MIM#614727 Review for gene: TMEM165 was set to AMBER Added comment: Affected individuals show psychomotor retardation and growth retardation, and most have short stature. Other features include dysmorphism, hypotonia, eye abnormalities, acquired microcephaly, hepatomegaly, and skeletal dysplasia. Serum transferrin analysis shows a CDG type II pattern Rx D-galactose (single paper, 2 unrelated patients and an in vitro study) ?inadequete evidence for treatment? Might need to check with JC if we would offer it maybe include Sources: Expert list |
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| BabyScreen+ newborn screening v0.1989 | IARS |
Zornitza Stark gene: IARS was added gene: IARS was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: IARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IARS were set to 27426735; 34194004 Phenotypes for gene: IARS were set to Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, MIM#617093 Review for gene: IARS was set to AMBER Added comment: Established gene-disease association. Congenital, multi-system metabolic disorder. N=1 study of Isoleucine supplementation and protein fortification (2.5mg/kg/day, during illness 3.5 g/kg/day) with some clinical improvement. Sources: Expert list |
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| BabyScreen+ newborn screening v0.1982 | TRNT1 |
Lilian Downie gene: TRNT1 was added gene: TRNT1 was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: TRNT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRNT1 were set to PMID: 25193871, PMID: 23553769, PMID: 33936027, PMID: 26494905 Phenotypes for gene: TRNT1 were set to Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay MIM#616084 Review for gene: TRNT1 was set to AMBER Added comment: Onset infancy Strong gene disease association Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) is an autosomal recessive syndromic disorder characterized by onset of severe sideroblastic anemia in the neonatal period or infancy. Affected individuals show delayed psychomotor development with variable neurodegeneration. Recurrent periodic fevers without an infectious etiology occur throughout infancy and childhood; immunologic work-up shows B-cell lymphopenia and hypogammaglobulinemia. Other more variable features include sensorineural hearing loss, retinitis pigmentosa, nephrocalcinosis, and cardiomyopathy. Death in the first decade may occur (summary by Wiseman et al., 2013). Bone marrow transplant (hematopoietic stem cell transplantation (HSCT)), replacement immunoglobulin treatment Allelic disease: Retinitis pigmentosa and erythrocytic microcytosis MIM#616959. Also AR. DeLuca et al. (2016) concluded that hypomorphic TRNT1 mutations can cause a recessive disease that is almost entirely limited to the retina - this has teenage onset and is not treatable. can we exclude these variants? Sources: Expert list |
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| BabyScreen+ newborn screening v0.1977 | HSD11B2 |
Zornitza Stark gene: HSD11B2 was added gene: HSD11B2 was added to Baby Screen+ newborn screening. Sources: Expert list treatable, endocrine tags were added to gene: HSD11B2. Mode of inheritance for gene: HSD11B2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: HSD11B2 were set to Apparent mineralocorticoid excess, MIM# 218030; MONDO:0009025 Review for gene: HSD11B2 was set to GREEN Added comment: Apparent mineralocorticoid excess (AME) is an autosomal recessive form of low-renin hypertension associated with low aldosterone, metabolic alkalosis, hypernatremia, and hypokalemia. The disorder is due to a congenital defect in 11-beta-hydroxysteroid dehydrogenase type II (HSD11B2) activity, resulting in decreased conversion of biologically active cortisol to inactive cortisone; this defect allows cortisol to act as a ligand for the mineralocorticoid receptor, resulting in sodium retention and volume expansion. There is a favorable therapeutic response to spironolactone. More than 10 unrelated families reported. Onset is usually in infancy or early childhood. Non-genetic confirmatory testing: aldosterone, renin, potassium levels Sources: Expert list |
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| BabyScreen+ newborn screening v0.1974 | UMPS |
Lilian Downie changed review comment from: megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001). Treat uridine Very rare only 20 cases but treatable. Sources: Expert list; to: megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001). Better check with John who wrote the paper!! PMID: 25030255 Treat uridine Very rare only 20 cases but treatable. Sources: Expert list |
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| BabyScreen+ newborn screening v0.1974 | UMPS |
Lilian Downie gene: UMPS was added gene: UMPS was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: UMPS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UMPS were set to PMID: 9042911, PMID: 28205048, PMID: 25757096, PMID: 33489760 Phenotypes for gene: UMPS were set to Orotic aciduria MIM#258900 Review for gene: UMPS was set to GREEN Added comment: megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001). Treat uridine Very rare only 20 cases but treatable. Sources: Expert list |
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| BabyScreen+ newborn screening v0.1952 | WNK4 |
Lilian Downie gene: WNK4 was added gene: WNK4 was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: WNK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: WNK4 were set to PMID: 22073419, PMID: 31795491, PMID: 10869238, Phenotypes for gene: WNK4 were set to Pseudohypoaldosteronism, type IIB MIM#614491 Review for gene: WNK4 was set to GREEN Added comment: Hyperkalaemia and hypertension Hypercalciuria Hypocalcaemia Decreased bone mineral density Renal calcium stones Treatable with thiazide diuretics Variable age of onset from infancy to adulthood but highly effective treatment so leaning toward include. Sources: Expert list |
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| BabyScreen+ newborn screening v0.1952 | ZBTB24 |
Lilian Downie gene: ZBTB24 was added gene: ZBTB24 was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: ZBTB24 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZBTB24 were set to PMID: 28128455, 21906047, 21596365, 23486536 Phenotypes for gene: ZBTB24 were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 2 MIM#614069 Review for gene: ZBTB24 was set to AMBER Added comment: INfant onset Agammaglobulinemia, facial anomalies, and mental retardation. Facial anomalies included broad, flat nasal bridge, hypertelorism, and epicanthal folds. Treat immunoglobulin and bone marrow transplant however, this only treats the immune deficiency Consider exclusion due to untreatable ID phenotype? Sources: Expert list |
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| BabyScreen+ newborn screening v0.1834 | WT1 |
Zornitza Stark changed review comment from: Rated as 'moderate actionability' in paediatric patients by ClinGen. Individuals with germline WT1 pathogenic variants are more likely to have bilateral or multicentric tumors and to develop tumors at an early age. The median age of diagnosis is between 3 and 4 years and both kidneys are affected in ~5% of children. Significantly more females than males have the bilateral disease. Adult forms are very rare. In the majority of cases, the prognosis is favorable with a survival rate of over 90%. The goal of surveillance in individuals with a genetic predisposition to WT is to detect tumors while they are low-stage and require less treatment compared to advanced-stage tumors. Surveillance is not a one-time event and should continue through the period of risk. WTs can double in size every week, leading to the recommendation that evaluation with abdominal ultrasound be performed every 3-4 months, with and no less frequently than 3 times a year, until age five years. Even at this frequency, occasional tumors may present clinically between scans and families should be made aware of this. However, there is no evidence to suggest that such tumors have a worse outcome. No evidence was found on the effectiveness of surveillance in children with WT due to WT1 pathogenic variants. In addition, there is no clear evidence that surveillance results in a significant decrease in mortality or tumor stage generally. However, tumors detected by surveillance would be anticipated to be on average smaller than tumors that present clinically. There have been three small retrospective evaluations of WT surveillance published, only one of which reported a significant difference in stage distribution between screened and unscreened individuals. This report was a case series of children with Beckwith-Wiedemann syndrome and idiopathic hemihypertropy, where 0/12 screened children with WT had late-stage disease and 25/59 (42%) of unscreened children had late-stage WT (p<0.003). In addition, in Germany, where abdominal ultrasound in children is common and 10% of WT are diagnosed prior to symptoms, there are some data to suggest that asymptomatic tumors are of lower stage than those present due to clinical symptoms. Penetrance is unclear. For review.; to: Rated as 'moderate actionability' in paediatric patients by ClinGen. Individuals with germline WT1 pathogenic variants are more likely to have bilateral or multicentric tumors and to develop tumors at an early age. The median age of diagnosis is between 3 and 4 years and both kidneys are affected in ~5% of children. Significantly more females than males have the bilateral disease. Adult forms are very rare. In the majority of cases, the prognosis is favorable with a survival rate of over 90%. The goal of surveillance in individuals with a genetic predisposition to WT is to detect tumors while they are low-stage and require less treatment compared to advanced-stage tumors. Surveillance is not a one-time event and should continue through the period of risk. WTs can double in size every week, leading to the recommendation that evaluation with abdominal ultrasound be performed every 3-4 months, with and no less frequently than 3 times a year, until age five years. Even at this frequency, occasional tumors may present clinically between scans and families should be made aware of this. However, there is no evidence to suggest that such tumors have a worse outcome. No evidence was found on the effectiveness of surveillance in children with WT due to WT1 pathogenic variants. In addition, there is no clear evidence that surveillance results in a significant decrease in mortality or tumor stage generally. However, tumors detected by surveillance would be anticipated to be on average smaller than tumors that present clinically. There have been three small retrospective evaluations of WT surveillance published, only one of which reported a significant difference in stage distribution between screened and unscreened individuals. This report was a case series of children with Beckwith-Wiedemann syndrome and idiopathic hemihypertropy, where 0/12 screened children with WT had late-stage disease and 25/59 (42%) of unscreened children had late-stage WT (p<0.003). In addition, in Germany, where abdominal ultrasound in children is common and 10% of WT are diagnosed prior to symptoms, there are some data to suggest that asymptomatic tumors are of lower stage than those present due to clinical symptoms. |
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| BabyScreen+ newborn screening v0.1821 | RET | Zornitza Stark Tag for review was removed from gene: RET. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1821 | RET |
Zornitza Stark changed review comment from: Established gene-disease associations. Assessed as 'strong actionability' in paediatric patients by ClinGen. Onset of MEN2A is typically prior to age 35, usually between ages 5 and 25. MTC is generally the first manifestation in MEN2A with probands presenting with a neck mass or neck pain. Metastatic spread is common. MTC is the most common cause of death in patients with MEN2A. PHEOs usually present after MTC or concomitantly but are the first manifestation in 13-27% of individuals; they occur in about 50% of individuals. PHEOs are diagnosed at an earlier age, have subtler symptoms, and are more likely to be bilateral than sporadic tumors, with malignant transformation occurring in about 4% of cases. Even without malignant progression, PHEOs can be lethal from intractable hypertension or anesthesia-induced hypertensive crises. Depending on the risk category of the RET pathogenic variant, PHEOs have been observed as early as 5 years of age. For MEN2A children with a “high-risk” pathogenic variant, patients should undergo annual ultrasound and screening for increased calcitonin levels starting at 3 years of age and proceed to thyroidectomy when elevated levels are detected or at 5 years of age. For patients with a “moderate-risk” pathogenic variant, considering the clinical variability of disease expression in family members in this category, annual physical examination, cervical US, and measurement of serum calcitonin levels, should begin at 5 years of age. Biochemical surveillance for PHPT should begin at 11 years and 16 years of age for patients with high- and moderate-risk variants, respectively; this screening is recommended annually for “high-risk” patients and at least every 2-3 years in “moderate-risk” patients. Biochemical screening for PHEO should begin at age 11 for patients with high-risk variants and age 16 for patients with moderate-risk variants. For review: actionable in first 5 years of life?; to: Established gene-disease associations. Assessed as 'strong actionability' in paediatric patients by ClinGen. Onset of MEN2A is typically prior to age 35, usually between ages 5 and 25. MTC is generally the first manifestation in MEN2A with probands presenting with a neck mass or neck pain. Metastatic spread is common. MTC is the most common cause of death in patients with MEN2A. PHEOs usually present after MTC or concomitantly but are the first manifestation in 13-27% of individuals; they occur in about 50% of individuals. PHEOs are diagnosed at an earlier age, have subtler symptoms, and are more likely to be bilateral than sporadic tumors, with malignant transformation occurring in about 4% of cases. Even without malignant progression, PHEOs can be lethal from intractable hypertension or anesthesia-induced hypertensive crises. Depending on the risk category of the RET pathogenic variant, PHEOs have been observed as early as 5 years of age. For MEN2A children with a “high-risk” pathogenic variant, patients should undergo annual ultrasound and screening for increased calcitonin levels starting at 3 years of age and proceed to thyroidectomy when elevated levels are detected or at 5 years of age. For patients with a “moderate-risk” pathogenic variant, considering the clinical variability of disease expression in family members in this category, annual physical examination, cervical US, and measurement of serum calcitonin levels, should begin at 5 years of age. Biochemical surveillance for PHPT should begin at 11 years and 16 years of age for patients with high- and moderate-risk variants, respectively; this screening is recommended annually for “high-risk” patients and at least every 2-3 years in “moderate-risk” patients. Biochemical screening for PHEO should begin at age 11 for patients with high-risk variants and age 16 for patients with moderate-risk variants. For review: some actionability in first 5 years, variants can be stratified in terms of risk. |
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| BabyScreen+ newborn screening v0.1753 | OAT |
Zornitza Stark gene: OAT was added gene: OAT was added to gNBS. Sources: ClinGen for review, treatable, metabolic tags were added to gene: OAT. Mode of inheritance for gene: OAT was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: OAT were set to Gyrate atrophy of choroid and retina with or without ornithinemia MIM#258870 Review for gene: OAT was set to GREEN Added comment: Rated as 'moderate actionability' in paediatric patients by ClinGen. GA due to deficiency of the enzyme ornithine aminotransferase (OAT) is characterized by a triad of progressive chorioretinal degeneration, early cataract formation, and type II muscle fiber atrophy. GA first presents as night blindness and constriction of the visual field caused by sharply demarcated circular areas of chorioretinal atrophy in the periphery. Atrophic areas progressively increase, coalesce, and spread towards the macula leading to central visual loss and blindness (vision less than 20/200). Age at diagnosis ranges from 1 month to 44 years. The condition is characterized by the development of chorioretinal atrophic patches that start in the mid-peripheral retina in the first decade of life. Myopia, night blindness, changes in the macula (including cystic changes), and visual field affection usually start in the first or second decade. Most patients with GA have posterior subcapsular cataracts by the end of the second decade. Irreversible loss of vision and blindness generally occurs between 40 and 55 years of age but is highly variable. Treatment of GA consists mainly of dietary modifications to help lower elevated systemic ornithine levels. Restriction of dietary arginine, a precursor of ornithine, appears to have therapeutic value. Pediatric patients undergoing arginine restriction should receive enough calories in their diet supplemented by essential amino acids, vitamins, and minerals to avoid malnutrition and excessive break down of endogenous proteins. A long-term observational study of 27 patients with GA, 17 who complied with the arginine-restricted diet and 10 who were noncompliant, found that at 14 years follow-up the rates of vision loss were significantly slower in the compliant group for 3 of the 4 outcome measures, when adjusted for age. Sources: ClinGen |
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| BabyScreen+ newborn screening v0.1728 | RPE65 |
Zornitza Stark gene: RPE65 was added gene: RPE65 was added to gNBS. Sources: ClinGen for review, treatable, ophthalmological tags were added to gene: RPE65. Mode of inheritance for gene: RPE65 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: RPE65 were set to Leber congenital amaurosis 2 MIM#204100; Retinitis pigmentosa 20 MIM#613794 Review for gene: RPE65 was set to GREEN Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen. Biallelic RPE65 mutation-associated retinal dystrophy is a form of IRD caused by biallelic pathogenic variants in RPE65; it presents as a spectrum of disease with variable age of onset and progression of vision loss. Common clinical findings across the spectrum include night blindness, progressive loss of visual fields and loss of central vision. In LCA, night blindness often occurs from birth. Characteristically, these patients have residual cone-mediated vision in the first to third decades with progressive visual field loss until complete blindness is observed, most often in mid- to late-adulthood. A range of age of onset has been described for night blindness in RP, but it typically onsets in later childhood. In December 2017, the FDA approved LUXTURNA (voretigene neparvovec-rzyl) gene therapy for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. The FDA’s conclusion of efficacy is based on improvement in a functional vision score over 1 year in a single open-label controlled Phase 3 study of 31 affected patients. The average age of the 31 randomized patients was 15 years (range 4 to 44 years), including 64% pediatric subjects (n=20, age from 4 to 17 years) and 36% adults (n=11). Functional vision was scored by a patient’s ability to navigate a course in various luminance levels. Using both treated eyes of the 21 subjects in the LUXTURNA treatment group, 11 (52%) had a clinically meaningful score improvement, while only one of the ten (10%) subjects in the control group had a clinically meaningful score improvement. Using the first treated eye only, 15/21 (71%) had a clinically meaningful score improvement, while no comparable score improvement was observed in controls. Other secondary clinical outcomes were also examined. Analysis of white light full-field light sensitivity threshold testing showed statistically significant improvement at 1 year in the LUXTURNA treatment group compared to the control group. The change in visual acuity was not significantly different between the LUXTURNA and control groups. LUXTURNA is administered subretinally by injection. Per the FDA package insert, the most common adverse reactions (incidence ≥ 5%) in the clinical trials for LUXTURNA included conjunctival hyperemia, cataract, increased intraocular pressure, retinal tear, dellen (thinning of the corneal stroma), and macular hole. Several other ocular adverse effects were also reported, including risk of endophthalmitis. Safety data was included on the basis of 41 patients (81 eyes). For review: availability of therapy? Sources: ClinGen |
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| BabyScreen+ newborn screening v0.1712 | RET | Zornitza Stark Marked gene: RET as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1712 | RET | Zornitza Stark Gene: ret has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1710 | COL9A1 |
David Amor changed review comment from: Gene-disease association: strong but rare, prbably <1% of Sticller syndrome; Van Camp et al. (2006) described a consanguineous Moroccan family in which 4 of 10 sibs had features characteristic of Stickler syndrome, including moderate to severe sensorineural hearing loss, moderate to high myopia with vitreoretinopathy, and epiphyseal dysplasia. Nikopoulos et al. (2011) reported 2 sisters in a Turkish family and 1 boy in a Moroccan family with features of autosomal recessive Stickler syndrome. All 3 individuals had myopia, vitreous changes, sensorineural hearing loss, and epiphyseal dysplasia. They also had exudative rhegmatogenous retinal detachment. Severity: moderate-severe Age of onset: congenital Non-molecular confirmatory testing: Affected individuals have moderate-to-severe sensorineural hearing loss, moderate-to-high myopia with vitreoretinopathy, cataracts, and epiphyseal dysplasia Treatment: as per other Stickler syndrome; to: Gene-disease association: strong but rare, prbably <1% of Sticller syndrome; Van Camp et al. (2006) described a consanguineous Moroccan family in which 4 of 10 sibs had features characteristic of Stickler syndrome, including moderate to severe sensorineural hearing loss, moderate to high myopia with vitreoretinopathy, and epiphyseal dysplasia. Nikopoulos et al. (2011) reported 2 sisters in a Turkish family and 1 boy in a Moroccan family with features of autosomal recessive Stickler syndrome. All 3 individuals had myopia, vitreous changes, sensorineural hearing loss, and epiphyseal dysplasia. They also had exudative rhegmatogenous retinal detachment. Severity: moderate-severe Age of onset: congenital Non-molecular confirmatory testing: Affected individuals have moderate-to-severe sensorineural hearing loss, moderate-to-high myopia with vitreoretinopathy, cataracts, and epiphyseal dysplasia Treatment: as per other Stickler syndrome |
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| BabyScreen+ newborn screening v0.1685 | CASR |
Zornitza Stark changed review comment from: AD hypoCa: Established gene-disease association. Congenital onset. Treatment: Thiazide diuretics, calcium, calcitriol. Non-genetic confirmatory testing: parathyroid hormone level, urinary calcium excretion, serum calcium.; to: AD hypoCa: Established gene-disease association. Congenital onset. Treatment: Thiazide diuretics, calcium, calcitriol. Non-genetic confirmatory testing: parathyroid hormone level, urinary calcium excretion, serum calcium. AD/AR hyperparathyroidism: established gene-disease association. Congenital onset. Treatment: bisphosphonate, parathyroidectomy, cinacalcet Non-genetic confirmatory testing: Ca, PTH. |
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| BabyScreen+ newborn screening v0.1685 | CASR |
Zornitza Stark changed review comment from: Established gene-disease association. Congenital onset. Treatment: Thiazide diuretics, calcium, calcitriol. Non-genetic confirmatory testing: parathyroid hormone level, urinary calcium excretion, serum calcium.; to: AD hypoCa: Established gene-disease association. Congenital onset. Treatment: Thiazide diuretics, calcium, calcitriol. Non-genetic confirmatory testing: parathyroid hormone level, urinary calcium excretion, serum calcium. |
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| BabyScreen+ newborn screening v0.1684 | CASR |
Zornitza Stark changed review comment from: Treatment: Thiazide diuretics, calcium, calcitriol; to: Established gene-disease association. Congenital onset. Treatment: Thiazide diuretics, calcium, calcitriol. Non-genetic confirmatory testing: parathyroid hormone level, urinary calcium excretion, serum calcium. |
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| BabyScreen+ newborn screening v0.1681 | COL4A5 |
Zornitza Stark changed review comment from: Well established gene-disease association. Natural history: In males, truncating variants in COL4A5 are associated with an earlier age at onset of kidney failure; risk of ESRD before age 30 is estimated as 90% for large rearrangements and pathogenic nonsense and frameshift variants, 70% for splice variants, and 50% for missense variants. In males, progressive SNHL is usually present by late childhood or early adolescence, and interior lenticous typically becomes apparent in late adolescence or early adulthood. In females, renal disease ranges from asymptomatic disease to lifelong microhematuria to renal failure at a young age. In females, progressive SNHL is typically later in life, lenticonus may not occur, and central retinopathy is rare. Assessed as 'strongly actionable' in paediatric patients by ClinGen. Treatment: ACE inhibitors alter long-term outcomes. Males with XLAS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria. Guidelines differ slightly for the initiation of treatment in females with XLAS; one guideline recommends initiation of treatment at onset of microalbuminuria while a second recommends initiation at onset of microalbuminuria, hypertension, or renal impairment. For review: screen both males and females?; to: Well established gene-disease association. Natural history: In males, truncating variants in COL4A5 are associated with an earlier age at onset of kidney failure; risk of ESRD before age 30 is estimated as 90% for large rearrangements and pathogenic nonsense and frameshift variants, 70% for splice variants, and 50% for missense variants. In males, progressive SNHL is usually present by late childhood or early adolescence, and interior lenticous typically becomes apparent in late adolescence or early adulthood. In females, renal disease ranges from asymptomatic disease to lifelong microhematuria to renal failure at a young age. In females, progressive SNHL is typically later in life, lenticonus may not occur, and central retinopathy is rare. Assessed as 'strongly actionable' in paediatric patients by ClinGen. Treatment: ACE inhibitors alter long-term outcomes. Males with XLAS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria. Guidelines differ slightly for the initiation of treatment in females with XLAS; one guideline recommends initiation of treatment at onset of microalbuminuria while a second recommends initiation at onset of microalbuminuria, hypertension, or renal impairment. |
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| BabyScreen+ newborn screening v0.1606 | PPT1 | John Christodoulou reviewed gene: PPT1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 21990111; Phenotypes: neurodegeneration, seizures, ataxia, optic atrophy, retinal abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1606 | POMT2 | Zornitza Stark Phenotypes for gene: POMT2 were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 MIM# 613158 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1604 | POMT2 | Zornitza Stark reviewed gene: POMT2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 613158; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1604 | POMGNT1 | Zornitza Stark Phenotypes for gene: POMGNT1 were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 MIM#614830; Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8 MIM#618135; Retinitis pigmentosa 76, MIM# 617123 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1602 | POMGNT1 | Zornitza Stark reviewed gene: POMGNT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 MIM#614830, Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8 MIM#618135, Retinitis pigmentosa 76 617123; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1593 | POMT1 | Zornitza Stark Phenotypes for gene: POMT1 were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1; Walker-Warburg syndrome to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 613155; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1591 | POMT1 | Zornitza Stark reviewed gene: POMT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 613155, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1591 | PQBP1 | Zornitza Stark Phenotypes for gene: PQBP1 were changed from Mental retardation to Renpenning syndrome, MIM#309500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1534 | TBC1D24 | Seb Lunke Phenotypes for gene: TBC1D24 were changed from Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures syndrome to DOORS syndrome MIM#220500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1480 | RB1 | Zornitza Stark Phenotypes for gene: RB1 were changed from Retinoblastoma to Retinoblastoma, MIM# 180200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1479 | RB1 | Zornitza Stark reviewed gene: RB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinoblastoma, MIM# 180200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1458 | RET |
Zornitza Stark Tag for review tag was added to gene: RET. Tag cancer tag was added to gene: RET. Tag treatable tag was added to gene: RET. |
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| BabyScreen+ newborn screening v0.1458 | RET | Zornitza Stark reviewed gene: RET: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple endocrine neoplasia IIA, MIM# 171400, Multiple endocrine neoplasia IIB, MIM# 162300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1456 | REN |
Zornitza Stark changed review comment from: Established gene-disease association. Presents as fetal anuria leading to perinatal death. No specific treatment.; to: Established gene-disease association. Bi-allelic LOF variants cause renal tubular dysgenesis, which presents as fetal anuria leading to perinatal death.. Mono-allelic variants, likely through a different mechanism (mostly missense) cause tubulointerstitial disease. More severe phenotype associated with variants that are located in the protein leader peptide and affecting its co-translational insertion in the endoplasmic reticulum (ER). No specific treatment for either. |
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| BabyScreen+ newborn screening v0.1455 | RETREG1 | Zornitza Stark Marked gene: RETREG1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1455 | RETREG1 | Zornitza Stark Gene: retreg1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1455 | RETREG1 | Zornitza Stark Phenotypes for gene: RETREG1 were changed from MONDO:0013142; Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115 to Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1454 | RETREG1 | Zornitza Stark Classified gene: RETREG1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1454 | RETREG1 | Zornitza Stark Gene: retreg1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1453 | RETREG1 | Zornitza Stark reviewed gene: RETREG1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1434 | RPGR | Zornitza Stark Phenotypes for gene: RPGR were changed from Retinitis pigmentosa to Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness, MIM# 300455 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1432 | RPGR | Zornitza Stark reviewed gene: RPGR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness, MIM# 300455; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1379 | RS1 | Zornitza Stark Phenotypes for gene: RS1 were changed from Retinoschisis, X linked to Retinoschisis, MIM#312700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1377 | RS1 | Zornitza Stark reviewed gene: RS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinoschisis, MIM#312700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1363 | SLC9A6 | Seb Lunke Phenotypes for gene: SLC9A6 were changed from Christianson syndrome to Mental retardation, X-linked syndromic, Christianson type, MIM# 300243 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1361 | SLC9A6 | Seb Lunke reviewed gene: SLC9A6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked syndromic, Christianson type, MIM# 300243; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1359 | SLC7A7 |
Seb Lunke edited their review of gene: SLC7A7: Added comment: Established gene-disease association. Childhood onset, multi-system disorder Treatment: protein restriction, carnitine, citrulline, lysine supplementation, sodium benzoate Non-genetic confirmatory test: 24-hour urinary excretion of cationic amino acids; Changed publications: 20301535 |
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| BabyScreen+ newborn screening v0.1272 | HSD17B10 | John Christodoulou reviewed gene: HSD17B10: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 22127393; Phenotypes: cardiomyopathy, early-onset intractable seizures, progressive choreoathetosis, spastic tetraplegia, optic atrophy, retinal degeneration, intellectual disability; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1253 | SLC9A3 |
Seb Lunke gene: SLC9A3 was added gene: SLC9A3 was added to gNBS. Sources: Literature for review tags were added to gene: SLC9A3. Mode of inheritance for gene: SLC9A3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SLC9A3 were set to Diarrhoea 8, secretory sodium, congenital, MiM# 616868 Review for gene: SLC9A3 was set to AMBER Added comment: Established gene-disease association. Childhood onset, congenital diarrhea. ?severity Treatment: sodium, bicarbonate Non-genetic confirmatory test: fecal sodium concentration Sources: Literature |
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| BabyScreen+ newborn screening v0.1166 | SLC26A3 | Seb Lunke Phenotypes for gene: SLC26A3 were changed from Chloride diarrhea, congenital, Finnish type to Diarrhoea 1, secretory chloride, congenital, MIM# 214700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1165 | SLC26A3 | Seb Lunke reviewed gene: SLC26A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diarrhoea 1, secretory chloride, congenital, MIM# 214700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1151 | COL11A1 |
Zornitza Stark changed review comment from: Mono-allelic variants in this gene cause Stickler syndrome, as well as isolated post-lingual deafness, and the rare Marshall syndrome. There is some genotype-phenotype correlation. Treatment: ocular surveillance and surgery to prevent retinal detachment For review; to: Mono-allelic variants in this gene cause Stickler syndrome, as well as isolated post-lingual deafness, and the rare Marshall syndrome. There is some genotype-phenotype correlation. Treatment: ocular surveillance and surgery to prevent retinal detachment. Usually after age 2-3 years. Discussed with ophthalmology: would start glaucoma surveillance in first year of life. |
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| BabyScreen+ newborn screening v0.1151 | COL2A1 |
Zornitza Stark changed review comment from: Variants in this gene are associated with a range of skeletal phenotypes. Onset and severity can be variable. Treatment: surveillance and prophylactic retinal laser treatment to prevent retinal detachment. For review.; to: Variants in this gene are associated with a range of skeletal phenotypes. Onset and severity can be variable. Treatment: surveillance and prophylactic retinal laser treatment to prevent retinal detachment. This is usually after the age of 2-3 years. Discussed with ophthalmology, would start glaucoma surveillance in the first year of life. |
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| BabyScreen+ newborn screening v0.1075 | KRT14 | Zornitza Stark Phenotypes for gene: KRT14 were changed from Epidermolysis bullosa simplex to Epidermolysis bullosa simplex, recessive 1, 601001; Dermatopathia pigmentosa reticularis, 125595; Epidermolysis bullosa simplex, Dowling-Meara type, 131760; Epidermolysis bullosa simplex, Koebner type, 131900; Epidermolysis bullosa simplex, Weber-Cockayne type, 131800; Naegeli-Franceschetti-Jadassohn syndrome, 161000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1072 | KRT14 | Zornitza Stark reviewed gene: KRT14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epidermolysis bullosa simplex, recessive 1, 601001, Dermatopathia pigmentosa reticularis, 125595, Epidermolysis bullosa simplex, Dowling-Meara type, 131760, Epidermolysis bullosa simplex, Koebner type, 131900, Epidermolysis bullosa simplex, Weber-Cockayne type, 131800, Naegeli-Franceschetti-Jadassohn syndrome, 161000; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1051 | DDB2 |
Zornitza Stark changed review comment from: Established gene-disease association. Range of age of onset, from childhood to adulthood. Most reported patients are adults, and this subtype which is generally milder. Treatment: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil. For review re age of onset.; to: Established gene-disease association. Range of age of onset, from childhood to adulthood. Most reported patients are adults, and this subtype which is generally milder. Treatment: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil. |
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| BabyScreen+ newborn screening v0.1051 | ERCC5 |
Zornitza Stark changed review comment from: Bi-allelic variants cause a range of DNA repair disorders. Variable severity and age of onset of manifestations. Some features are treatable: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil. For discussion.; to: Bi-allelic variants cause a range of DNA repair disorders. Variable severity and age of onset of manifestations. Some features are treatable: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil. |
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| BabyScreen+ newborn screening v0.1047 | ERCC2 |
Zornitza Stark changed review comment from: Bi-allelic variants in this gene cause a range of conditions, including COFS, trichothiodystrophy and XPE. DNA repair disorder. Some features are treatable: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil. For discussion.; to: Bi-allelic variants in this gene cause a range of conditions, including COFS, trichothiodystrophy and XPE. DNA repair disorder. Some features are treatable: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil. |
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| BabyScreen+ newborn screening v0.1044 | FAM161A | Zornitza Stark Phenotypes for gene: FAM161A were changed from Retinal dystrophy to Retinitis pigmentosa 28, 606068 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1042 | FAM161A | Zornitza Stark reviewed gene: FAM161A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 28, 606068; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1025 | FGD1 | Zornitza Stark Phenotypes for gene: FGD1 were changed from Aarskog-Scott syndrome to Aarskog-Scott syndrome, MIM # 305400; Mental retardation, X-linked syndromic 16, MIM# 305400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1023 | FGD1 | Zornitza Stark reviewed gene: FGD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Aarskog-Scott syndrome, MIM # 305400, Mental retardation, X-linked syndromic 16, MIM# 305400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.950 | GGCX | John Christodoulou edited their review of gene: GGCX: Changed phenotypes: bleeding disorder, pseudoxanthoma elasticum, pigmentary retinopathy, congenital heart disease | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.862 | PCBD1 |
Zornitza Stark changed review comment from: Well established gene-disease association. Presents in the neonatal period: characterized by mild transient hyperphenylalaninemia often detected by newborn screening. Patients also show increased excretion of 7-biopterin. Affected individuals are asymptomatic and show normal psychomotor development, although transient neurologic deficits in infancy have been reported. Patients may also develop hypomagnesemia and non-autoimmune diabetes mellitus during puberty. ; to: Well established gene-disease association. Presents in the neonatal period: characterized by mild transient hyperphenylalaninemia often detected by newborn screening. Patients also show increased excretion of 7-biopterin. Affected individuals are asymptomatic and show normal psychomotor development, although transient neurologic deficits in infancy have been reported. Patients may also develop hypomagnesemia and non-autoimmune diabetes mellitus during puberty. |
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| BabyScreen+ newborn screening v0.841 | COL7A1 | Zornitza Stark Phenotypes for gene: COL7A1 were changed from Epidermolysis bullosa dystrophica to EBD inversa, MIM# 226600; EBD, Bart type MIM# 132000 EBD, localisata variant; Epidermolysis bullosa dystrophica, MIM# 131750; Epidermolysis bullosa dystrophica, 226600; Epidermolysis bullosa pruriginosa 604129; Epidermolysis bullosa, pretibial, MIM# 131850; Transient bullous of the newborn 131705 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.838 | COL7A1 | Zornitza Stark reviewed gene: COL7A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: EBD inversa, MIM# 226600, EBD, Bart type MIM# 132000 EBD, localisata variant, Epidermolysis bullosa dystrophica, MIM# 131750, Epidermolysis bullosa dystrophica, 226600, Epidermolysis bullosa pruriginosa 604129, Epidermolysis bullosa, pretibial, MIM# 131850, Transient bullous of the newborn 131705; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.811 | TTR | Zornitza Stark Phenotypes for gene: TTR were changed from Amyloidosis, hereditary, transthyretin-related to Amyloidosis, hereditary, transthyretin-related MIM#105210 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.802 | TTR | Lilian Downie reviewed gene: TTR: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20301373, PMID: 3032328, PMID: 29972753, PMID: 29972757; Phenotypes: Amyloidosis, hereditary, transthyretin-related MIM#105210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.791 | CTC1 | Zornitza Stark Phenotypes for gene: CTC1 were changed from Coats plus syndrome to Cerebroretinal microangiopathy with calcifications and cysts, MIM# 612199 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.789 | CTC1 | Zornitza Stark reviewed gene: CTC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebroretinal microangiopathy with calcifications and cysts, MIM# 612199; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.744 | PAK3 | Zornitza Stark Phenotypes for gene: PAK3 were changed from Mental retardation syndrome, X-linked to Mental retardation syndrome, X-linked 30, MIM#300558 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.721 | PCBD1 |
Zornitza Stark changed review comment from: Well established gene-disease association. Presents in the neonatal period: characterized by mild transient hyperphenylalaninemia often detected by newborn screening. Patients also show increased excretion of 7-biopterin. Affected individuals are asymptomatic and show normal psychomotor development, although transient neurologic deficits in infancy have been reported. Patients may also develop hypomagnesemia and non-autoimmune diabetes mellitus during puberty. For review; to: Well established gene-disease association. Presents in the neonatal period: characterized by mild transient hyperphenylalaninemia often detected by newborn screening. Patients also show increased excretion of 7-biopterin. Affected individuals are asymptomatic and show normal psychomotor development, although transient neurologic deficits in infancy have been reported. Patients may also develop hypomagnesemia and non-autoimmune diabetes mellitus during puberty. |
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| BabyScreen+ newborn screening v0.719 | PHYH | John Christodoulou reviewed gene: PHYH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: retinitis pigmentosa with night blindness, cataracts, polyneuropathy including sensory disturbances, cerebellar ataxia, anosmia, progressive hearing loss; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.719 | PHKG2 | John Christodoulou reviewed gene: PHKG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30659246, https://www.ncbi.nlm.nih.gov/books/NBK55061/#gsd9.Summary; Phenotypes: hepatomegaly, hypotonia, growth retardation, hypoglycaemia, fasting ketosis, cirrhosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.719 | PHGDH | John Christodoulou reviewed gene: PHGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: growth retardation, congenital microcephaly, hypogonadism, hypertonia, severe ID, epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.664 | ETFB |
Zornitza Stark changed review comment from: Well established gene-disease association. Glutaric aciduria II (GA2) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I in that multiple acyl-CoA dehydrogenase deficiencies result in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. The heterogeneous clinical features of MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. Symptoms and age at presentation of late-onset MADD are highly variable and characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occurs. The organic aciduria in those with the late-onset form of MADD is often intermittent and only evident during periods of illness or catabolic stress. Treatment: riboflavin, carnitine, glycine, Coenzyme Q10 supplementation, fat restriction, avoidance of fasting, and a diet rich in carbohydrates Non-genetic confirmatory tests: plasma acylcarnitine profile, urine organic acid analysis; to: Well established gene-disease association. Glutaric aciduria II (GA2) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I in that multiple acyl-CoA dehydrogenase deficiencies result in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. The heterogeneous clinical features of MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. Symptoms and age at presentation of late-onset MADD are highly variable and characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occurs. The organic aciduria in those with the late-onset form of MADD is often intermittent and only evident during periods of illness or catabolic stress. Treatment: riboflavin, carnitine, glycine, Coenzyme Q10 supplementation, fat restriction, avoidance of fasting, and a diet rich in carbohydrates Non-genetic confirmatory tests: plasma acylcarnitine profile, urine organic acid analysis Predominantly neonatal onset. |
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| BabyScreen+ newborn screening v0.644 | SETBP1 | Seb Lunke Phenotypes for gene: SETBP1 were changed from Schinzel-Giedion syndrome to Schinzel-Giedion midface retraction syndrome, MIM# 269150 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.642 | SETBP1 | Seb Lunke reviewed gene: SETBP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Schinzel-Giedion midface retraction syndrome, MIM# 269150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.627 | CEP83 | Zornitza Stark reviewed gene: CEP83: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephronophthisis 18, MIM# 615862, MONDO:0014374, Retinal dystrophy, ID; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.599 | VLDLR | Zornitza Stark Phenotypes for gene: VLDLR were changed from Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1 to Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion MIM#224050 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.588 | VLDLR | Lilian Downie reviewed gene: VLDLR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion MIM#224050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.583 | FUCA1 | John Christodoulou reviewed gene: FUCA1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 33266441; Phenotypes: neurodegneration, coarse facial features, grow retardation, dysostosis multiplex, angiokeratomata, recurrent URTIs; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.568 | CASK | Zornitza Stark Phenotypes for gene: CASK were changed from Mental retardation and microcephaly with pontine and cerebellar hypoplasia to FG syndrome 4 MIM#300422; Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749; Mental retardation, with or without nystagmus MIM#300422 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.565 | CASK | Zornitza Stark reviewed gene: CASK: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: FG syndrome 4 MIM#300422, Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749, Mental retardation, with or without nystagmus MIM#300422; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.503 | WHRN |
Lilian Downie commented on gene: WHRN: Definitive gene disease association Usher, moderate evidence it can also cause a non syndromic hearing loss phenotype. Congenital hearing impairment, childhood onset visual loss Treatment supportive, clinical trials for retinitis pigmentosa *I think we should keep hearing loss genes on as it's part of traditional newborn screening* |
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| BabyScreen+ newborn screening v0.474 | OFD1 | Zornitza Stark Phenotypes for gene: OFD1 were changed from Oral-facial-digital syndrome to Retinitis pigmentosa 23, MIM# 300424; Joubert syndrome 10, MIM# 300804; Orofaciodigital syndrome I, MIM# 311200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.472 | OFD1 | Zornitza Stark reviewed gene: OFD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 23, MIM# 300424, Joubert syndrome 10, MIM# 300804, Orofaciodigital syndrome I, MIM# 311200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.436 | NHEJ1 | Zornitza Stark reviewed gene: NHEJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.315 | MECP2 | Zornitza Stark Phenotypes for gene: MECP2 were changed from Rett syndrome to MECP2-related disorders Rett syndrome, MIM# 312750 Mental retardation, X-linked, syndromic 13, MIM# 300055 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.312 | MECP2 | Zornitza Stark reviewed gene: MECP2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: MECP2-related disorders Rett syndrome, MIM# 312750 Mental retardation, X-linked, syndromic 13, MIM# 300055; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.274 | ETFA |
Zornitza Stark changed review comment from: Well established gene-disease association. Glutaric aciduria II (GA2) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I in that multiple acyl-CoA dehydrogenase deficiencies result in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. The heterogeneous clinical features of MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. Symptoms and age at presentation of late-onset MADD are highly variable and characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occurs. The organic aciduria in those with the late-onset form of MADD is often intermittent and only evident during periods of illness or catabolic stress. Treatment: riboflavin, carnitine, glycine, Coenzyme Q10 supplementation, fat restriction, avoidance of fasting, and a diet rich in carbohydrates, D,L-3-hydroxybutyrate Non-genetic confirmatory tests: plasma acylcarnitine profile, urine organic acid analysis; to: Well established gene-disease association. Glutaric aciduria II (GA2) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I in that multiple acyl-CoA dehydrogenase deficiencies result in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. The heterogeneous clinical features of MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. Symptoms and age at presentation of late-onset MADD are highly variable and characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occurs. The organic aciduria in those with the late-onset form of MADD is often intermittent and only evident during periods of illness or catabolic stress. Treatment: riboflavin, carnitine, glycine, Coenzyme Q10 supplementation, fat restriction, avoidance of fasting, and a diet rich in carbohydrates, D,L-3-hydroxybutyrate (PMID 31904027) Non-genetic confirmatory tests: plasma acylcarnitine profile, urine organic acid analysis |
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| BabyScreen+ newborn screening v0.274 | NHEJ1 | David Amor reviewed gene: NHEJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.271 | HADHA |
Zornitza Stark changed review comment from: Well established gene-disease association. Clinical presentation is characterised by early-onset cardiomyopathy, hypoglycaemia, neuropathy, and pigmentary retinopathy, and sudden death Treatment: IV glucose during acute episodes, avoid fasting, carnitine, restrict LCFA, bezafibrate, triheptanoin; to: Well established gene-disease association. Clinically, classic trifunctional protein deficiency can be classified into 3 main clinical phenotypes: neonatal onset of a severe, lethal condition resulting in sudden unexplained infant death, infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal myopathy. Treatment: IV glucose during acute episodes, avoid fasting, carnitine, restrict LCFA, bezafibrate, triheptanoin |
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| BabyScreen+ newborn screening v0.270 | MECP2 | David Amor reviewed gene: MECP2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Rett syndrome; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.218 | LARGE1 | Zornitza Stark Phenotypes for gene: LARGE1 were changed from Walker-Warburg syndrome to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, MIM# 613154; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6, MIM# 608840 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.216 | LARGE1 | Zornitza Stark reviewed gene: LARGE1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, MIM# 613154, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6, MIM# 608840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.205 | LRP5 | David Amor edited their review of gene: LRP5: Changed phenotypes: osteoporosis-pseudoglioma syndrome, cause exudative vireoretinopathy, osteopetrosis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.199 | LAMP2 | David Amor reviewed gene: LAMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Danon disease - cardiomyopathy, retinal disease, cognitive dysfunction; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.160 | ATRX | Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome to Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Intellectual disability-hypotonic facies syndrome, X-linked, MIM# 309580 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.158 | ATRX | Zornitza Stark reviewed gene: ATRX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Alpha-thalassemia/mental retardation syndrome, MIM# 301040, Intellectual disability-hypotonic facies syndrome, X-linked, MIM# 309580; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.119 | AVPR2 |
Zornitza Stark changed review comment from: Well established gene-disease association. Onset in infancy. Causes severe dehydration, can be life-threatening. Treatment: hydration, low-salt, low-protein diet, thiazide diuretics, amiloride, indomethacin. Clinical trials.; to: Well established gene-disease association. Onset in infancy. Causes severe dehydration, can be life-threatening. Treatment: hydration, low-salt, low-protein diet, thiazide diuretics, amiloride, indomethacin. Clinical trials. Around 10% of variants are large deletions. |
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| BabyScreen+ newborn screening v0.65 | AK2 | Zornitza Stark Phenotypes for gene: AK2 were changed from Reticular dysgenesis, MIM# 267500 to Reticular dysgenesis, MIM# 267500; MONDO:0009973 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.63 | AK2 | Zornitza Stark reviewed gene: AK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19043416, 19043417; Phenotypes: Reticular dysgenesis, MIM# 267500, MONDO:0009973; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.49 | ABCA4 | Zornitza Stark Phenotypes for gene: ABCA4 were changed from Stargardt disease to Cone-rod dystrophy 3, 604116; Fundus flavimaculatus, 248200; Retinal dystrophy, early-onset severe, 248200; Retinitis pigmentosa 19, 601718; Stargardt disease 1, 248200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.47 | ABCA4 | Zornitza Stark reviewed gene: ABCA4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cone-rod dystrophy 3, 604116, Fundus flavimaculatus, 248200, Retinal dystrophy, early-onset severe, 248200, Retinitis pigmentosa 19, 601718, Stargardt disease 1, 248200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.0 | ZNF674 |
Zornitza Stark gene: ZNF674 was added gene: ZNF674 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: ZNF674 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ZNF674 were set to Mental retardation |
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| BabyScreen+ newborn screening v0.0 | TBCE |
Zornitza Stark gene: TBCE was added gene: TBCE was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TBCE were set to Hypoparathyroidism retardation dysmorphism syndrome |
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| BabyScreen+ newborn screening v0.0 | SLC4A10 |
Zornitza Stark gene: SLC4A10 was added gene: SLC4A10 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: SLC4A10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: SLC4A10 were set to Epilepsy & mental retardation |
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| BabyScreen+ newborn screening v0.0 | FSCN2 |
Zornitza Stark gene: FSCN2 was added gene: FSCN2 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: FSCN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: FSCN2 were set to Retinitis pigmentosa |
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| BabyScreen+ newborn screening v0.0 | BNC2 |
Zornitza Stark gene: BNC2 was added gene: BNC2 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: BNC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: BNC2 were set to Total anomalous pulmonary venous return |
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| BabyScreen+ newborn screening v0.0 | ACO2 |
Zornitza Stark gene: ACO2 was added gene: ACO2 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: ACO2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ACO2 were set to Cerebellar-retinal degeneration, infantile |
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| BabyScreen+ newborn screening v0.0 | VLDLR |
Zornitza Stark gene: VLDLR was added gene: VLDLR was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: VLDLR was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: VLDLR were set to Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1 |
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| BabyScreen+ newborn screening v0.0 | TTR |
Zornitza Stark gene: TTR was added gene: TTR was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: TTR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: TTR were set to Amyloidosis, hereditary, transthyretin-related |
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| BabyScreen+ newborn screening v0.0 | TBC1D24 |
Zornitza Stark gene: TBC1D24 was added gene: TBC1D24 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: TBC1D24 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TBC1D24 were set to Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures syndrome |
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| BabyScreen+ newborn screening v0.0 | RS1 |
Zornitza Stark gene: RS1 was added gene: RS1 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: RS1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: RS1 were set to Retinoschisis, X linked |
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| BabyScreen+ newborn screening v0.0 | RPGR |
Zornitza Stark gene: RPGR was added gene: RPGR was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: RPGR was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: RPGR were set to Retinitis pigmentosa |
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| BabyScreen+ newborn screening v0.0 | RETREG1 |
Zornitza Stark gene: RETREG1 was added gene: RETREG1 was added to gNBS. Sources: Expert Review Green,BabySeq Category C gene Mode of inheritance for gene: RETREG1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RETREG1 were set to 31737055; 31596031; 24327336; 19838196 Phenotypes for gene: RETREG1 were set to MONDO:0013142; Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115 |
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| BabyScreen+ newborn screening v0.0 | RET |
Zornitza Stark gene: RET was added gene: RET was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: RET was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: RET were set to Multiple endocrine neoplasia IIB; Multiple endocrine neoplasia IIA |
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| BabyScreen+ newborn screening v0.0 | RB1 |
Zornitza Stark gene: RB1 was added gene: RB1 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: RB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: RB1 were set to Retinoblastoma |
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| BabyScreen+ newborn screening v0.0 | PQBP1 |
Zornitza Stark gene: PQBP1 was added gene: PQBP1 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: PQBP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: PQBP1 were set to Mental retardation |
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| BabyScreen+ newborn screening v0.0 | PAK3 |
Zornitza Stark gene: PAK3 was added gene: PAK3 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: PAK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: PAK3 were set to Mental retardation syndrome, X-linked |
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| BabyScreen+ newborn screening v0.0 | NHEJ1 |
Zornitza Stark gene: NHEJ1 was added gene: NHEJ1 was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: NHEJ1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NHEJ1 were set to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM#611291 |
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| BabyScreen+ newborn screening v0.0 | MECP2 |
Zornitza Stark gene: MECP2 was added gene: MECP2 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: MECP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: MECP2 were set to Rett syndrome |
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| BabyScreen+ newborn screening v0.0 | FAM161A |
Zornitza Stark gene: FAM161A was added gene: FAM161A was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: FAM161A was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FAM161A were set to Retinal dystrophy |
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| BabyScreen+ newborn screening v0.0 | CEP83 |
Zornitza Stark gene: CEP83 was added gene: CEP83 was added to gNBS. Sources: Expert Review,Expert Review Green Mode of inheritance for gene: CEP83 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CEP83 were set to 33938610; 24882706 Phenotypes for gene: CEP83 were set to Nephronophthisis 18, MIM# 615862; ID; MONDO:0014374; Retinal dystrophy |
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| BabyScreen+ newborn screening v0.0 | CASK |
Zornitza Stark gene: CASK was added gene: CASK was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: CASK was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: CASK were set to Mental retardation and microcephaly with pontine and cerebellar hypoplasia |
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| BabyScreen+ newborn screening v0.0 | ATRX |
Zornitza Stark gene: ATRX was added gene: ATRX was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: ATRX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ATRX were set to Alpha-thalassemia/mental retardation syndrome |
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| BabyScreen+ newborn screening v0.0 | AK2 |
Zornitza Stark gene: AK2 was added gene: AK2 was added to gNBS. Sources: BeginNGS,Expert Review Green Mode of inheritance for gene: AK2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: AK2 were set to Reticular dysgenesis, MIM# 267500 |
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