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| Dystonia - complex v0.284 | ATP5A1 |
Zornitza Stark gene: ATP5A1 was added gene: ATP5A1 was added to Dystonia - complex. Sources: Literature new gene name tags were added to gene: ATP5A1. Mode of inheritance for gene: ATP5A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP5A1 were set to 34483339; 34954817; 40859057 Phenotypes for gene: ATP5A1 were set to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A (MIM#620358), AD Review for gene: ATP5A1 was set to GREEN Added comment: At least 12 individuals reported with de novo missense variants in this gene, several recurrent. PMIDs: 34483339, 34954817: 6xde novo patients 4 with Arg207His, 1 Arg182Gln 1 Ser346Phe. All Arg207His patients were neonates with failure to thrive, hyperammonemia, lactic acidosis, and respiratory defects in fibroblasts, major symptoms remitted with treatment by late infancy, and at age 14mo to 3yrs growth and development were normal. Other 2 patients are 17yo with ID, ataxia, spastic paraparesis and dystonia, and a 12yo with psychomotor retardation, spastic tetraparesis, generalised dystonia, absent speech, swallowing problems, and increased blood lactate concentrations. And an internal VCGS patient Arg182Gln (variant also seen in a different patient above) with ID, muscular hypotonia, clinodactyly of the 5th finger, and dysmorphic facial features, proteomics showed decreased ATP5F1A and a complex V deficiency. There is also an alternative change at this residue in the DECIPHER cohort Arg182Pro de novo in an individual with a neurodevelopmental disorder. PMID: 40672495: 6x de novo individuals - 4 variants p.Arg182Gln, p.Ser346Phe, p.Pro331Leu, and p.Leu109Ser - with complex but overlapping neurological phenotypes including developmental delays, intellectual disability, pyramidal tract dysfunction, and dystonia. In vivo functional studies in C. elegans were performed for three of the variants, showing growth defects and disruption of mitochondrial function (measured by mitochondrial stress). Authors suggest a dominant negative mechanism. Sources: Literature |
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| Dystonia - complex v0.242 | ATM | Sangavi Sivagnanasundram reviewed gene: ATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301790, 29436738, 30504431, 22345219; Phenotypes: ataxia telangiectasia MONDO:0008840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia - complex v0.207 | WARS2 |
Zornitza Stark gene: WARS2 was added gene: WARS2 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: WARS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WARS2 were set to 29120065; 31970218; 34890876; 28236339; 28650581; 28905505; 30920170 Phenotypes for gene: WARS2 were set to Parkinsonism-dystonia 3, childhood-onset, MIM# 619738; Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, MIM# 617710 Review for gene: WARS2 was set to GREEN Added comment: Childhood-onset parkinsonism-dystonia-3 (PKDYS3) is an autosomal recessive neurodegenerative disorder with onset in infancy or early childhood. Affected individuals present with progressive movement abnormalities, including parkinsonism with tremor, dystonia, myoclonus ataxia, and hyperkinetic movements such as ballismus. The parkinsonism features may be responsive to treatment with levodopa, although many patients develop levodopa-induced dyskinesia. Some patients may have mild cognitive impairment or psychiatric disturbances. 8 individuals from 4 families reported. NEMMLAS is an autosomal recessive multisystemic disorder characterized by delayed psychomotor development, intellectual disability, and abnormal motor function, including hypotonia, dystonia, ataxia, and spasticity. Patient tissues may show deficiencies in one or more of the mitochondrial oxidative phosphorylation (OXPHOS) enzymes, but this is not a constant finding. 12 individuals from 8 unrelated families reported. It is unclear whether these are two distinct disorders or whether they represent a spectrum of severity for a single condition. Sources: Literature |
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| Dystonia - complex v0.177 | VPS41 | Zornitza Stark edited their review of gene: VPS41: Added comment: Another 9 individuals from 5 unrelated families reported. Affected individuals were born after uneventful pregnancies and presented in most cases early in life with developmental delay. Various degrees of ataxia, hypotonia, and dystonia were present in all affected individuals, preventing independent ambulation. Likewise, nystagmus was commonly described. In addition, all affected individuals displayed intellectual disability and speech delay, and one sib pair had treatment-resistant epilepsy.; Changed rating: GREEN; Changed publications: 32808683, 33764426 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia - complex v0.61 | SLC18A2 |
Zornitza Stark gene: SLC18A2 was added gene: SLC18A2 was added to Dystonia - complex. Sources: Expert Review Mode of inheritance for gene: SLC18A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC18A2 were set to 23363473; 31240161; 26497564 Phenotypes for gene: SLC18A2 were set to Parkinsonism-dystonia, infantile, 2, MIM# 618049 Review for gene: SLC18A2 was set to GREEN Added comment: At least three unrelated families reported, potential treatment implications. Associated with intellectual disability and epilepsy as well as prominent movement disorder. Sources: Expert Review |
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| Dystonia - complex v0.0 | ATM |
Bryony Thompson gene: ATM was added gene: ATM was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: ATM was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ATM were set to Ataxia telangiectasia; Dystonia |
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