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| Mendeliome v1.2178 | CTGF | Bryony Thompson Phenotypes for gene: CTGF were changed from Kyphomelic dysplasia to Kyphomelic dysplasia MONDO:0008881; Spondyloepimetaphyseal dysplasia MONDO:0100510 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2168 | CTGF | Sangavi Sivagnanasundram edited their review of gene: CTGF: Changed phenotypes: Kyphomelic dysplasia, skeletal dysplasia MONDO:0018230 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2166 | CTGF |
Sangavi Sivagnanasundram changed review comment from: CCN2 is the new HGNC approved name. PMID: 39506047 Three individuals from two unrelated consanguineous families presented with short stature, facial dysmorphism and kyphomelic skeletal dysplasia. A rare missense variant in family 1 (Cys148Tyr) and novel frameshift variant (Pro260LeufsTer7) in family 2 was identified in homozygous state. Zebrafish model was also conducted that showed altered body curvature and impaired cartilage formation in craniofacial region resulting in either bent of missing tails. A missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5. Sources: Literature; to: CCN2 is the new HGNC approved name. PMID: 39506047 Three individuals from two unrelated consanguineous families presented with short stature, facial dysmorphism and kyphomelic skeletal dysplasia. A rare missense variant in family 1 (Cys148Tyr) and novel frameshift variant (Pro260LeufsTer7) in family 2 was identified in homozygous state. Zebrafish model was also conducted that showed altered body curvature and impaired cartilage formation in craniofacial region resulting in either bent or missing tails. A missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5. Sources: Literature |
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| Mendeliome v1.2166 | CTGF |
Sangavi Sivagnanasundram gene: CTGF was added gene: CTGF was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CTGF was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CTGF were set to 39506047 Phenotypes for gene: CTGF were set to Kyphomelic dysplasia Review for gene: CTGF was set to AMBER Added comment: CCN2 is the new HGNC approved name. PMID: 39506047 Three individuals from two unrelated consanguineous families presented with short stature, facial dysmorphism and kyphomelic skeletal dysplasia. A rare missense variant in family 1 (Cys148Tyr) and novel frameshift variant (Pro260LeufsTer7) in family 2 was identified in homozygous state. Zebrafish model was also conducted that showed altered body curvature and impaired cartilage formation in craniofacial region resulting in either bent of missing tails. A missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5. Sources: Literature |
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| Mendeliome v1.1501 | CAMK2D |
Elena Savva gene: CAMK2D was added gene: CAMK2D was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CAMK2D were set to 38272033 Phenotypes for gene: CAMK2D were set to Neurodevelopmental disorder (MONDO#0700092), CAMK2D-related Added comment: PMID: 38272033 - 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old - Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological - Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5) Sources: Literature |
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| Mendeliome v1.1423 | KIF5B | Zornitza Stark Phenotypes for gene: KIF5B were changed from Skeletal dysplasia, MONDO:0018230, KIF5B-related; Kyphomelic dysplasia to osteogenesis imperfecta, MONDO:0019019; Skeletal dysplasia, MONDO:0018230, KIF5B-related; Kyphomelic dysplasia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1042 | TBX6 | Zornitza Stark Phenotypes for gene: TBX6 were changed from Spondylocostal dysostosis 5, 122600 to Spondylocostal dysostosis 5, 122600; Mayer-Rokitansky-Küster-Hauser syndrome, MONDO:0017771, TBX6-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1010 | TBX6 | Chirag Patel reviewed gene: TBX6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36112137, 36161696; Phenotypes: Mayer-Rokitansky-Küster-Hauser syndrome, Combined skeletal-kidney dysplasia syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.853 | RARA |
Zornitza Stark commented on gene: RARA: PMID: 37086723 identified a recurrent, heterozygous de novo missense variant in the RARA gene - c.865G>A; (p.Gly289Arg) - in two unrelated individuals. The variant is absent from gnomAD, highly conserved, major grantham score (125) and is located in the hormone receptor domain (DECIPHER). Both individuals had severe craniosynostosis (sagittal or bicoronal). Other shared phenotypic features included: - Limb anomalies (rocker-bottom feet, bowing of the legs, and short upper/lower limbs) - Additional craniofacial manifestations(microtia, conductive hearing loss, ankyloglossia, esotropia, hypoplastic nasal bones, and oligodontia) - Other additional anomalies included renal dysplasia with cysts, tracheomalacia, pulmonary arterial hypertension, developmental delays, hypotonia, cryptorchidism, seizures and adrenal insufficiency. The authors postulate a gain of function mechanism. No functional studies provided. The gene encodes the retinoic acid receptor. Overlapping phenotypic features in these 2 affected individuals with retinoic acid embryopathy noted by the authors. |
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| Mendeliome v1.850 | RARA |
Zornitza Stark edited their review of gene: RARA: Added comment: PMID: 37086723 identified a recurrent, heterozygous de novo missense variant in the RARA gene - c.865G>A; (p.Gly289Arg) - in two unrelated individuals. The variant is absent from gnomAD, highly conserved, major grantham score (125) and is located in the hormone receptor domain (DECIPHER). Both individuals had severe craniosynostosis (sagittal or bicoronal). Other shared phenotypic features included: - Limb anomalies (rocker-bottom feet, bowing of the legs, and short upper/lower limbs) - Additional craniofacial manifestations(microtia, conductive hearing loss, ankyloglossia, esotropia, hypoplastic nasal bones, and oligodontia) - Other additional anomalies included renal dysplasia with cysts, tracheomalacia, pulmonary arterial hypertension, developmental delays, hypotonia, cryptorchidism, seizures and adrenal insufficiency. The authors postulate a gain of function mechanism. No functional studies provided. The gene encodes the retinoic acid receptor. Overlapping phenotypic features in these 2 affected individuals with retinoic acid embryopathy noted by the authors.; Changed rating: AMBER; Changed publications: 31343737, 37086723; Changed phenotypes: Craniosynostosis - MONDO:0015469, Syndromic chorioretinal coloboma; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
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| Mendeliome v1.291 | LGI3 | Zornitza Stark Phenotypes for gene: LGI3 were changed from Global developmental delay; Intellectual disability; Distal deformities; Diminished reflexes; Facial myokymia; Hyporeflexia/areflexi to Neurodevelopmental disorder, MONDO:0700092, LGI3-related; Global developmental delay; Intellectual disability; Distal deformities; Diminished reflexes; Facial myokymia; Hyporeflexia/areflexi | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.285 | LGI3 | Melanie Marty edited their review of gene: LGI3: Changed phenotypes: Global developmental delay, Intellectual disability, Distal deformities, Diminished reflexes, Facial myokymia, Hyporeflexia/areflexia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.283 | LGI3 |
Melanie Marty gene: LGI3 was added gene: LGI3 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LGI3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LGI3 were set to PMID: 35948005 Phenotypes for gene: LGI3 were set to Global developmental delay; Intellectual disability; Distal deformities; Diminished reflexes; Facial myokymia; Hyporeflexia/areflexi Review for gene: LGI3 was set to GREEN Added comment: Sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. Lgi3-null mice showed reduced and mis-local-ized Kv1 channel complexes in myelinated peripheral axons. Sources: Literature |
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| Mendeliome v1.276 | ADAMTS15 |
Naomi Baker changed review comment from: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: ontractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5). Sources: Literature; to: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: contractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5). Sources: Literature |
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| Mendeliome v1.276 | ADAMTS15 |
Naomi Baker gene: ADAMTS15 was added gene: ADAMTS15 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ADAMTS15 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS15 were set to PMID: 35962790 Phenotypes for gene: ADAMTS15 were set to Arthrogryposis (MONDO:0008779), ADMATS15-related Review for gene: ADAMTS15 was set to GREEN Added comment: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: ontractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5). Sources: Literature |
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| Mendeliome v1.266 | KIF5B | Zornitza Stark Phenotypes for gene: KIF5B were changed from Skeletal dysplasia, MONDO:0018230 to Skeletal dysplasia, MONDO:0018230, KIF5B-related; Kyphomelic dysplasia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.265 | KIF5B | Zornitza Stark Phenotypes for gene: KIF5B were changed from Kyphomelic dysplasia, no OMIM # to Skeletal dysplasia, MONDO:0018230 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.257 | KIF5B |
Chirag Patel gene: KIF5B was added gene: KIF5B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIF5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KIF5B were set to PMID: 35342932 Phenotypes for gene: KIF5B were set to Kyphomelic dysplasia, no OMIM # Review for gene: KIF5B was set to GREEN Added comment: 4 individuals with Kyphomelic dysplasia (severe bowing of the limbs, sharp angulation of the femora and humeri, short stature, narrow thorax, distinctive facial features, and neonatal respiratory distress. WES found de novo heterozygous missense variants in KIF5B encoding kinesin-1 heavy chain. All variants involved conserved amino acids in or close to the ATPase activity-related motifs in the catalytic motor domain of the KIF5B protein. No functional studies of variants. Previously 2 animal model experiments showed that loss of function of KIF5B can cause kyphomelic dysplasia. First, chondrocyte-specific knockout of Kif5b in mice was shown to produce a disorganized growth plate, leading to bone deformity. Second, double mutants disrupting the two zebrafish kif5b caused abnormal skeletal morphogenesis and the curvature of Meckel's and ceratohyal cartilages. Sources: Literature |
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| Mendeliome v0.13260 | PLOD1 | Zornitza Stark edited their review of gene: PLOD1: Changed phenotypes: Ehlers-Danlos syndrome, kyphoscoliotic type, 1, MIM# 225400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13260 | PLOD1 | Zornitza Stark Phenotypes for gene: PLOD1 were changed from to Ehlers-Danlos syndrome, kyphoscoliotic type, 1, MIM## 225400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13257 | PLOD1 | Zornitza Stark reviewed gene: PLOD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28306225; Phenotypes: Ehlers-Danlos syndrome, kyphoscoliotic type, 1.<O<# 225400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12233 | BLOC1S6 | Bryony Thompson reviewed gene: BLOC1S6: Rating: GREEN; Mode of pathogenicity: None; Publications: 32245340, 33543539, 29054114, 26575419, 22461475, 10610180; Phenotypes: Hermansky-Pudlak syndrome 9, MIM# 614171; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11880 | NOG | Zornitza Stark Phenotypes for gene: NOG were changed from to Brachydactyly, type B2 - MIM#611377; Multiple synostoses syndrome 1 (MIM#186500); Stapes ankylosis with broad thumbs and toes (MIM#184460); Symphalangism, proximal, 1A (MIM#185800); Tarsal-carpal coalition syndrome (MIM#186570) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11860 | NOG | Krithika Murali reviewed gene: NOG: Rating: GREEN; Mode of pathogenicity: None; Publications: 11846737, 18440889, 12089654, 10080184, 15066478, 22088931, 17381491; Phenotypes: Brachydactyly, type B2 - MIM#611377, Multiple synostoses syndrome 1 (MIM#186500), Stapes ankylosis with broad thumbs and toes (MIM#184460), Symphalangism, proximal, 1A (MIM#185800), Tarsal-carpal coalition syndrome (MIM#186570); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11346 | KCNA1 | Zornitza Stark Phenotypes for gene: KCNA1 were changed from to Episodic ataxia/myokymia syndrome, MIM# 160120; Epilepsy, MONDO:0005027, KCNA1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11172 | KY | Zornitza Stark Marked gene: KY as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11172 | KY | Zornitza Stark Gene: ky has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11172 | KY | Zornitza Stark Phenotypes for gene: KY were changed from to Myopathy, myofibrillar, 7, MIM#617114 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11171 | KY | Zornitza Stark Publications for gene: KY were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11170 | KY | Zornitza Stark Mode of inheritance for gene: KY was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11169 | KY | Zornitza Stark reviewed gene: KY: Rating: GREEN; Mode of pathogenicity: None; Publications: 11136708, 27485408, 27484770, 30591934; Phenotypes: Myopathy, myofibrillar, 7, MIM#617114; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11169 | KYNU | Zornitza Stark Marked gene: KYNU as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11169 | KYNU | Zornitza Stark Gene: kynu has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11169 | KYNU | Zornitza Stark Phenotypes for gene: KYNU were changed from to Hydroxykynureninuria MIM#236800; Vertebral, cardiac, renal, and limb defects syndrome 2 MIM#617661; Disorders of histidine, tryptophan or lysine metabolism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11168 | KYNU | Zornitza Stark Publications for gene: KYNU were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11167 | KYNU | Zornitza Stark Mode of inheritance for gene: KYNU was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11078 | AP3D1 | Zornitza Stark edited their review of gene: AP3D1: Added comment: Now four affected individuals from two unrelated families, with a mouse model that recapitulates the human phenotype.; Changed rating: GREEN; Changed publications: 26744459, 9697856, 30472485; Changed phenotypes: Hermansky-Pudlak syndrome 10, MIM# 617050, Oculocutaneous albinism, Severe neutropaenia, Recurrent infections, Seizures, Hearing loss, Neurodevelopmental delay | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10749 | PAX8 | Zornitza Stark Phenotypes for gene: PAX8 were changed from to Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia, MIM# 218700; Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10746 | PAX8 | Zornitza Stark reviewed gene: PAX8: Rating: GREEN; Mode of pathogenicity: None; Publications: 33434492, 9590296, 11232006, 15356023, 15718293; Phenotypes: Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia, MIM# 218700, Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10643 | TBX22 | Zornitza Stark Phenotypes for gene: TBX22 were changed from to Cleft palate with ankyloglossia, MIM# 303400; Abruzzo-Erickson syndrome, MIM# 302905 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10640 | TBX22 | Zornitza Stark reviewed gene: TBX22: Rating: GREEN; Mode of pathogenicity: None; Publications: 11559848, 12374769, 14729838, 17868388, 22784330, 22784330; Phenotypes: Cleft palate with ankyloglossia, MIM# 303400, Abruzzo-Erickson syndrome, MIM# 302905; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10184 | ADCY5 | Zornitza Stark Phenotypes for gene: ADCY5 were changed from Dyskinesia, familial, with facial myokymia, MIM# 606703; MONDO:0011707 to Dyskinesia, familial, with facial myokymia, MIM# 606703; MONDO:0011707; Hyperkinetic movement disorder with dyskinesia, myoclonus, chorea, and dystonia-2 (HYDMCD2), MIM#619647; Neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD), MIM#619651 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10181 | ADCY5 |
Zornitza Stark edited their review of gene: ADCY5: Added comment: Neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD) is an autosomal recessive complex neurologic disorder characterized by severe global developmental delay with axial hypotonia, impaired intellectual development, poor overall growth, and abnormal involuntary hyperkinetic movements, including dystonia, myoclonus, spasticity, and orofacial dyskinesia. It is the most severe manifestation of ADCY5-related dyskinetic disorders. Five individuals from 2 families reported. Autosomal recessive hyperkinetic movement disorder with dyskinesia, myoclonus, chorea, and dystonia-2 (HYDMCD2) is characterized by the onset of abnormal involuntary movements, mainly affecting the limbs and causing walking difficulties, in the first decade. The severity is variable; some patients have orofacial dyskinesia, resulting in speech difficulties, or develop neuropsychiatric features, including anxiety and social withdrawal. Cardiomyopathy has rarely been described and may be a manifestation of the disorder. Eight individuals from 2 families reported.; Changed publications: 22782511, 24700542, 33051786, 32647899, 33704598, 34631954, 28971144, 30975617; Changed phenotypes: Dyskinesia, familial, with facial myokymia, MIM# 606703, MONDO:0011707, Hyperkinetic movement disorder with dyskinesia, myoclonus, chorea, and dystonia-2 (HYDMCD2), MIM#619647, Neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD), MIM#619651; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Mendeliome v0.8732 | JAKMIP1 |
Seb Lunke gene: JAKMIP1 was added gene: JAKMIP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: JAKMIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: JAKMIP1 were set to 29158550; 26627310; 27799067 Phenotypes for gene: JAKMIP1 were set to Intellectual disability; Seizures Review for gene: JAKMIP1 was set to AMBER Added comment: Identified in two independent patients in the literature with a mouse model. Patient 1 (27799067) with developmental delay, speech delay, and cognitive impairment; self-injurious and aggressive behaviour, seizures, dysmorphic features. De-novo missense JAKMIP1 (p.D586H). Patient 2 (29158550) with feeding difficulties, hypotonia, epilepsy, severe ID, no active speech, kyphoscoliosis, constipation, autism, short stature. Splice variant c.1432-2A>G, no segregation or RNA data available. KO mouse model (27799067) displays social deficits, stereotyped activity, abnormal postnatal vocalizations, and other autistic-like behaviors. Sources: Literature |
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| Mendeliome v0.7795 | HPS6 | Zornitza Stark Phenotypes for gene: HPS6 were changed from to Hermansky-Pudlak syndrome 6, MIM# 614075; MONDO:0013558 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7792 | HPS6 | Zornitza Stark reviewed gene: HPS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 12548288, 17041891, 19843503; Phenotypes: Hermansky-Pudlak syndrome 6, MIM# 614075, MONDO:0013558; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7791 | HPS4 | Zornitza Stark Phenotypes for gene: HPS4 were changed from to Hermansky-Pudlak syndrome 4, MIM# 614073; MONDO:0013556 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7789 | HPS4 | Zornitza Stark reviewed gene: HPS4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11836498, 12664304; Phenotypes: Hermansky-Pudlak syndrome 4, MIM# 614073, MONDO:0013556; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7789 | HPS3 | Zornitza Stark Phenotypes for gene: HPS3 were changed from to Hermansky-Pudlak syndrome 3, MIM# 614072; MONDO:0013555 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7786 | HPS3 | Zornitza Stark reviewed gene: HPS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 11455388, 31880485, 31621111, 30990103; Phenotypes: Hermansky-Pudlak syndrome 3, MIM# 614072, MONDO:0013555; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7786 | HPS1 | Zornitza Stark Phenotypes for gene: HPS1 were changed from to Hermansky-Pudlak syndrome 1, MIM# 203300; MONDO:0008748 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7783 | HPS1 | Zornitza Stark reviewed gene: HPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9497254; Phenotypes: Hermansky-Pudlak syndrome 1, MIM# 203300, MONDO:0008748; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7749 | DTNBP1 | Zornitza Stark Phenotypes for gene: DTNBP1 were changed from to Hermansky-Pudlak syndrome 7, MIM# 614076; MONDO:0013559 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7746 | DTNBP1 | Zornitza Stark reviewed gene: DTNBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12923531, 23364359, 28259707, 30990103; Phenotypes: Hermansky-Pudlak syndrome 7, MIM# 614076, MONDO:0013559; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7746 | BLOC1S3 | Zornitza Stark Phenotypes for gene: BLOC1S3 were changed from to Hermansky-Pudlak syndrome 8, MIM# 614077; MONDO:0013560 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7743 | BLOC1S3 | Zornitza Stark reviewed gene: BLOC1S3: Rating: GREEN; Mode of pathogenicity: None; Publications: 16385460, 22709368, 32687635; Phenotypes: Hermansky-Pudlak syndrome 8, MIM# 614077, MONDO:0013560; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7743 | AP3B1 | Zornitza Stark Phenotypes for gene: AP3B1 were changed from to Hermansky-Pudlak syndrome 2, MIM# 608233; MONDO:0011997 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7740 | AP3B1 | Zornitza Stark reviewed gene: AP3B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10024875, 11809908, 14566336; Phenotypes: Hermansky-Pudlak syndrome 2, MIM# 608233, MONDO:0011997; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7403 | ADCY5 | Zornitza Stark Phenotypes for gene: ADCY5 were changed from to Dyskinesia, familial, with facial myokymia, MIM# 606703; MONDO:0011707 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7400 | ADCY5 | Zornitza Stark reviewed gene: ADCY5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22782511, 24700542, 33051786, 32647899, 33704598; Phenotypes: Dyskinesia, familial, with facial myokymia, MIM# 606703, MONDO:0011707; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7374 | KCNJ6 |
Zornitza Stark changed review comment from: Keppen-Lubinsky syndrome characterised by severely delayed psychomotor development, hypertonia, hyperreflexia, generalized lipodystrophy giving an aged appearance, and distinctive dysmorphic features, including microcephaly, prominent eyes, narrow nasal bridge, and open mouth. Three unrelated individuals reported with de novo variants in this gene (one recurred in 2), mouse model.; to: Keppen-Lubinsky syndrome characterised by severely delayed psychomotor development, hypertonia, hyperreflexia, generalized lipodystrophy giving an aged appearance, and distinctive dysmorphic features, including microcephaly, prominent eyes, narrow nasal bridge, and open mouth. Four unrelated individuals reported with de novo variants in this gene (one recurred in 2), mouse model. One of the individuals did not have lipodystrophy but had a prominent hyperkinetic movement disorder. |
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| Mendeliome v0.7374 | KCNJ6 | Zornitza Stark Phenotypes for gene: KCNJ6 were changed from to Keppen-Lubinsky syndrome, MIM# 614098; MONDO:0013572 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7371 | KCNJ6 | Zornitza Stark reviewed gene: KCNJ6: Rating: GREEN; Mode of pathogenicity: None; Publications: 25620207; Phenotypes: Keppen-Lubinsky syndrome, MIM# 614098, MONDO:0013572; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6876 | POLR3A |
Elena Savva commented on gene: POLR3A: c.1909+22G>A is a recurring variant that results in a leaky splice site Bi-allelic variants associated with Leukodystrophy and with Wiedemann-Rautenstrauch syndrome; note association between mono-allelic variants and susceptibility to severe VZV infection. Deep intronic variants commonly pathogenic No clear gen-phen correlation |
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| Mendeliome v0.6213 | BMP7 | Zornitza Stark Phenotypes for gene: BMP7 were changed from Non-syndromic metopic craniosynostosis; Congenital abnormalities of the kidneys and urinary tract to Non-syndromic metopic craniosynostosis; Congenital abnormalities of the kidneys and urinary tract; Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6211 | BMP7 | Zornitza Stark edited their review of gene: BMP7: Changed phenotypes: Non-syndromic metopic craniosynostosis, Congenital abnormalities of the kidneys and urinary tract, Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6143 | BLOC1S5 | Zornitza Stark Phenotypes for gene: BLOC1S5 were changed from Hermansky–Pudlak syndrome to Hermansky–Pudlak syndrome 11, MIM#619172 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6142 | BLOC1S5 | Zornitza Stark edited their review of gene: BLOC1S5: Changed phenotypes: Hermansky–Pudlak syndrome 11, MIM#619172 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5361 | KCNQ2 | Zornitza Stark Phenotypes for gene: KCNQ2 were changed from to Epileptic encephalopathy, early infantile, 7, 613720; Seizures, benign neonatal, 1, 121200; Myokymia, 121200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5357 | KCNQ2 | Elena Savva reviewed gene: KCNQ2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 25959266, 32917465, 24318194; Phenotypes: Epileptic encephalopathy, early infantile, 7, 613720, Seizures, benign neonatal, 1, 121200, Myokymia, 121200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4916 | FKBP14 | Zornitza Stark Phenotypes for gene: FKBP14 were changed from to Ehlers-Danlos syndrome, kyphoscoliotic type, 2, MIM# 614557 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4913 | FKBP14 | Zornitza Stark reviewed gene: FKBP14: Rating: GREEN; Mode of pathogenicity: None; Publications: 22265013, 24773188, 27149304, 31132235, 30561154, 28617417; Phenotypes: Ehlers-Danlos syndrome, kyphoscoliotic type, 2, MIM# 614557; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4668 | BLOC1S5 |
Zornitza Stark gene: BLOC1S5 was added gene: BLOC1S5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: BLOC1S5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BLOC1S5 were set to 32565547 Phenotypes for gene: BLOC1S5 were set to Hermansky–Pudlak syndrome Review for gene: BLOC1S5 was set to GREEN Added comment: 2 unrelated patients with mild oculocutaneous albinism, moderate bleeding diathesis, platelet aggregation deficit, and a dramatically decreased number of platelet dense granules, all signs compatible with HPS. Identified distinct homozygous variants in the BLOC1S5 gene (patient 1: deletion of exons 3 and 4, patient 2: 1-bp deletion in exon 4). Parental segregation confirmatory in patient 1, quantitative PCR analysis confirmatory in patient 2). Functional tests performed on platelets of one patient displayed an absence of the obligate multisubunit complex BLOC-1, showing that the variant disrupts BLOC1S5 function and impairs BLOC-1 assembly. Expression of the patient-derived BLOC1S5 deletion in nonpigmented murine Bloc1s5-/- melan-mu melanocytes failed to rescue pigmentation, the assembly of a functional BLOC-1 complex, and melanosome cargo trafficking, unlike the wild-type allele. Pathogenic variants in the genes encoding three other BLOC-1 subunits (DTNBP1, BLOC1S3, and BLOC1S6) underlie HPS types 7, 8, and 9 respectively. Sources: Literature |
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| Mendeliome v0.4536 | HPS5 | Zornitza Stark Phenotypes for gene: HPS5 were changed from to Hermansky-Pudlak syndrome 5 (MIM#614074) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4533 | HPS5 | Zornitza Stark reviewed gene: HPS5: Rating: GREEN; Mode of pathogenicity: None; Publications: 28296950, 32725903; Phenotypes: Hermansky-Pudlak syndrome 5 (MIM#614074); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3662 | RELN | Zornitza Stark Phenotypes for gene: RELN were changed from Lissencephaly 2 (Norman-Roberts type), MIM# 257320; ankylosing spondylitis to Lissencephaly 2 (Norman-Roberts type), MIM# 257320; {Epilepsy, familial temporal lobe, 7}, MIM# 616436; ankylosing spondylitis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3661 | RELN | Zornitza Stark Phenotypes for gene: RELN were changed from to Lissencephaly 2 (Norman-Roberts type), MIM# 257320; ankylosing spondylitis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3657 | RELN | Chern Lim reviewed gene: RELN: Rating: AMBER; Mode of pathogenicity: None; Publications: 32001840; Phenotypes: ankylosing spondylitis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3321 | CCDC174 |
Zornitza Stark gene: CCDC174 was added gene: CCDC174 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: CCDC174 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCDC174 were set to 26358778 Phenotypes for gene: CCDC174 were set to Hypotonia, infantile, with psychomotor retardation - IHPMR, 616816 Review for gene: CCDC174 was set to AMBER Added comment: Biallelic pathogenic CCDC174 variants cause Hypotonia, infantile, with psychomotor retardation - IHPMR (MIM 616816). Volodarsky et al [2015 - PMID: 26358778] describe 6 children from 2 unrelated families with - among others - severe hypotonia, psychomotor delay and abducens nerve palsy. All affected subjects were homozygous for a stoploss variant. Evidence from functional studies/animal model is provided supporting the role of the gene in this phenotype. Overall this gene can be considered for inclusion in the ID panel with amber rating (2 families, single founder variant, consistent phenotype, supportive studies) pending further reports. Sources: Expert Review |
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| Mendeliome v0.2685 | TNK2 | Zornitza Stark Phenotypes for gene: TNK2 were changed from to late onset infantile epilepsy; Mayer-Rokitansky-Küster-Hauser syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2680 | TNK2 | Elena Savva reviewed gene: TNK2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID 27977884, 23686771, 31517310; Phenotypes: late onset infantile epilepsy, Mayer-Rokitansky-Küster-Hauser syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2049 | BLOC1S6 | Zornitza Stark Phenotypes for gene: BLOC1S6 were changed from to Hermansky-Pudlak syndrome 9, MIM# 614171 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2045 | BLOC1S6 | Zornitza Stark reviewed gene: BLOC1S6: Rating: AMBER; Mode of pathogenicity: None; Publications: 22461475, 21665000, 32245340; Phenotypes: Hermansky-Pudlak syndrome 9, MIM# 614171; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1943 | AP3D1 |
Zornitza Stark gene: AP3D1 was added gene: AP3D1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: AP3D1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AP3D1 were set to 26744459; 9697856 Phenotypes for gene: AP3D1 were set to Hermansky-Pudlak syndrome 10, MIM# 617050; Oculocutaneous albinism; Severe neutropaenia; Recurrent infections; Seizures; Hearing loss; Neurodevelopmental delay Review for gene: AP3D1 was set to RED Added comment: Single family and a mouse model. Sources: Expert list |
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| Mendeliome v0.0 | KYNU |
Zornitza Stark gene: KYNU was added gene: KYNU was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: KYNU was set to Unknown |
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| Mendeliome v0.0 | KY |
Zornitza Stark gene: KY was added gene: KY was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: KY was set to Unknown |
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