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| Regression v0.567 | NAXE |
Zornitza Stark gene: NAXE was added gene: NAXE was added to Regression. Sources: Expert Review Mode of inheritance for gene: NAXE was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NAXE were set to 27122014; 27616477; 31758406 Phenotypes for gene: NAXE were set to Encephalopathy, progressive, early-onset, with brain oedema and/or leukoencephalopathy, MIM# 617186 Review for gene: NAXE was set to GREEN Added comment: Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL1) is an autosomal recessive severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration that is usually associated with a febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, respiratory insufficiency, and seizures, resulting in coma and death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions. More than 5 unrelated families reported. Sources: Expert Review |
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| Regression v0.464 | SLC25A42 |
Zornitza Stark gene: SLC25A42 was added gene: SLC25A42 was added to Regression. Sources: Expert Review founder tags were added to gene: SLC25A42. Mode of inheritance for gene: SLC25A42 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC25A42 were set to 26541337; 29327420; 29923093; 34258143 Phenotypes for gene: SLC25A42 were set to Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression , MIM#618416 Review for gene: SLC25A42 was set to GREEN Added comment: Recurrent metabolic crises with variable encephalomyopathic features and neurologic regression (MECREN) is an autosomal recessive metabolic disorder with a highly variable phenotype. Most affected individuals present in the first years of life with episodic lactic acidosis associated with illness or stress, resulting in transient or permanent neurologic dysfunction. Some patients may recover, whereas others show subsequent variable developmental regression of motor and cognitive skills. Other features may include dystonia, hypotonia with inability to sit or walk, seizures, and abnormal signals in the basal ganglia. Sixteen individuals reported, 14 with the same founder variant, c.871A > G:p.Asn291Asp. Two additional variants reported in another two individuals. Sources: Expert Review |
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| Regression v0.419 | NDUFAF4 |
Krithika Murali changed review comment from: 2 unrelated families reported with patient-specific functional evidence provided for each. Regression noted in one reported patient. Other reported family had two siblings unwell from birth with a relatively fulminant course. Another large family reported with recurrent decompensation episodes. PMID: 32949790 - report two siblings with facial dysmorphism and lactic acidosis diagnosed neonatally with subsequent fatal early encephalopathy with apneic episodes, irritability, central hypoventilation, liver involvement and hyperammonemia. Cerebral white matter anomalies reported in one patient and cardiomyopathy in the other. WES identified homozygous nonsense NDUFAF4 variants with absent NDUFAF4 expression in patient fibroblasts. OXPHOS assembly studies demonstrated almost undetectable levels of fully assembled complex I and complex I–containing supercomplexes and an abnormal accumulation of SCIII2IV1 supercomplexes. Morphologically, fibroblasts showed rounder mitochondria and a diminished degree of branching of the mitochondrial network. PMID: 28853723 - report one patient born at 38 weeks after IOL for IUGR. Presented age 7 months with developmental regression, growth failure and central hypotonia. Brain MRI revealed diffuse bilateral signal alterations in the basal ganglia and thalami and an EEG showed generalized slowing with multifocal spikes consistent with an epileptogenic focus. Homozygous missense NDUFAF4 variants identified. Lentiviral complementation of patient fibroblasts with wild-type NDUFAF4 rescued complex I deficiency and assembly defect PMID 18179882 - report multiple affected individuals from one family. Most presented soon after birth with severe metabolic acidosis and high plasma lactate levels. Patients who survived longer were repeatedly admitted because of exacerbation of the acidosis during intercurrent infections. One long-term survivor had profound ID. Seizures occurred in 2 individuals during decompensation episodes. Brain MRI of one patient at 16 months of age revealed severe atrophy of both gray and white matter, with demyelination, most prominent at the anterior aspects of the brain, leaving a cortical ribbon. At the occipito-parietal region there were subventricular cysts, emphasizing the ventricular walls. The cerebellum, basal ganglia, pons, and medulla were severely atrophic; to: 3 unrelated families reported with patient-specific functional evidence provided for each. Regression noted in one reported patient. Other reported family had two siblings unwell from birth with a relatively fulminant course. Another large family reported with fulminant neonatal course / longer-term survivors having recurrent decompensation episodes. PMID: 32949790 - report two siblings with facial dysmorphism and lactic acidosis diagnosed neonatally with subsequent fatal early encephalopathy with apneic episodes, irritability, central hypoventilation, liver involvement and hyperammonemia. Cerebral white matter anomalies reported in one patient and cardiomyopathy in the other. WES identified homozygous nonsense NDUFAF4 variants with absent NDUFAF4 expression in patient fibroblasts. OXPHOS assembly studies demonstrated almost undetectable levels of fully assembled complex I and complex I–containing supercomplexes and an abnormal accumulation of SCIII2IV1 supercomplexes. Morphologically, fibroblasts showed rounder mitochondria and a diminished degree of branching of the mitochondrial network. PMID: 28853723 - report one patient born at 38 weeks after IOL for IUGR. Presented age 7 months with developmental regression, growth failure and central hypotonia. Brain MRI revealed diffuse bilateral signal alterations in the basal ganglia and thalami and an EEG showed generalized slowing with multifocal spikes consistent with an epileptogenic focus. Homozygous missense NDUFAF4 variants identified. Lentiviral complementation of patient fibroblasts with wild-type NDUFAF4 rescued complex I deficiency and assembly defect PMID 18179882 - report multiple affected individuals from one family. Most presented soon after birth with severe metabolic acidosis and high plasma lactate levels. Patients who survived longer were repeatedly admitted because of exacerbation of the acidosis during intercurrent infections. One long-term survivor had profound ID. Seizures occurred in 2 individuals during decompensation episodes. Brain MRI of one patient at 16 months of age revealed severe atrophy of both gray and white matter, with demyelination, most prominent at the anterior aspects of the brain, leaving a cortical ribbon. At the occipito-parietal region there were subventricular cysts, emphasizing the ventricular walls. The cerebellum, basal ganglia, pons, and medulla were severely atrophic |
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| Regression v0.306 | GNAL | Zornitza Stark Marked gene: GNAL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Regression v0.306 | GNAL | Zornitza Stark Gene: gnal has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Regression v0.306 | GNAL | Zornitza Stark Phenotypes for gene: GNAL were changed from to Dystonia 25, MIM# 615073; MONDO:0014033 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Regression v0.305 | GNAL | Zornitza Stark Publications for gene: GNAL were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Regression v0.304 | GNAL | Zornitza Stark Mode of inheritance for gene: GNAL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Regression v0.303 | GNAL | Zornitza Stark Classified gene: GNAL as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Regression v0.303 | GNAL | Zornitza Stark Gene: gnal has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Regression v0.302 | GNAL | Zornitza Stark reviewed gene: GNAL: Rating: RED; Mode of pathogenicity: None; Publications: 23222958, 33175450, 32180288; Phenotypes: Dystonia 25, MIM# 615073, MONDO:0014033; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Regression v0.230 | LSM11 |
Ee Ming Wong gene: LSM11 was added gene: LSM11 was added to Regression. Sources: Literature Mode of inheritance for gene: LSM11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LSM11 were set to PMID: 33230297 Phenotypes for gene: LSM11 were set to type I interferonopathy Aicardi–Goutières syndrome Review for gene: LSM11 was set to RED gene: LSM11 was marked as current diagnostic Added comment: - Two affected siblings from a consanguineous family carrying a homozygous variant in LSM11 - Compared to control fibroblasts, patient fibroblasts were enriched for misprocessed forms of replication-dependent histone (RDH) mRNAs - Knockdown of LSM11 in THP-1 cells results in an increase in misprocessed RDH mRNA and interferon signaling (added as Red as per discussion with Seb) Sources: Literature |
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| Regression v0.0 | GNAL |
Zornitza Stark gene: GNAL was added gene: GNAL was added to Regression_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: GNAL was set to Unknown |
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