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| Dystonia and Chorea v0.335 | GPR88 |
Bryony Thompson gene: GPR88 was added gene: GPR88 was added to Dystonia and Chorea. Sources: Literature Mode of inheritance for gene: GPR88 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GPR88 were set to 27123486 Phenotypes for gene: GPR88 were set to chorea, childhood-onset, with psychomotor retardation MONDO:0014839 Review for gene: GPR88 was set to RED Added comment: Single consanguineous Palestinian family reported with a homozygous stopgain variant (c.873C>A, p.Cys291*) Sources: Literature |
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| Dystonia and Chorea v0.333 | PRNP |
Bryony Thompson gene: PRNP was added gene: PRNP was added to Dystonia and Chorea. Sources: Literature Mode of inheritance for gene: PRNP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PRNP were set to 30713928; 27400454 Phenotypes for gene: PRNP were set to Huntington disease-like 1 MONDO:0011299 Review for gene: PRNP was set to GREEN Added comment: Chorea can be feature of inherited prionopathies. Sources: Literature |
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| Dystonia and Chorea v0.323 | Bryony Thompson Copied gene THAP1 from panel Dystonia - isolated/combined | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.323 | THAP1 |
Bryony Thompson gene: THAP1 was added gene: THAP1 was added to Dystonia - complex. Sources: Expert Review Green,Royal Melbourne Hospital Mode of inheritance for gene: THAP1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: THAP1 were set to 21793105; 22377579; 36205328; 21425335; 20211909 Phenotypes for gene: THAP1 were set to Dystonia 6, torsion, 602629; Dystonia; MONDO:0011264 |
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| Dystonia and Chorea v0.322 | Bryony Thompson Copied gene TH from panel Dystonia - isolated/combined | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.322 | TH |
Bryony Thompson gene: TH was added gene: TH was added to Dystonia - complex. Sources: Expert Review Green,Royal Melbourne Hospital Mode of inheritance for gene: TH was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TH were set to Segawa syndrome, recessive, MIM# 605407; MONDO:0011551 |
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| Dystonia and Chorea v0.320 | SPR |
Bryony Thompson gene: SPR was added gene: SPR was added to Dystonia - complex. Sources: Expert Review Green,Royal Melbourne Hospital Mode of inheritance for gene: SPR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SPR were set to 11443547; 18502672; 22522443; 16532389; 31777525; 29147684; 28189489 Phenotypes for gene: SPR were set to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, MIM# 612716; MONDO:0012994 |
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| Dystonia and Chorea v0.317 | RELN |
Bryony Thompson gene: RELN was added gene: RELN was added to Dystonia - complex. Sources: Expert Review Red,Other Mode of inheritance for gene: RELN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RELN were set to 32334381; 25648840 Phenotypes for gene: RELN were set to Myoclonus-dystonia syndrome MONDO:0000903 |
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| Dystonia and Chorea v0.312 | PDE10A |
Bryony Thompson gene: PDE10A was added gene: PDE10A was added to Dystonia - complex. Sources: Expert Review Green,Expert list Mode of inheritance for gene: PDE10A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDE10A were set to PMID 27058447 Phenotypes for gene: PDE10A were set to Early onset chorea without epilepsy; infantile onset limb and orofacial dyskinesia (OMIM 616921) |
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| Dystonia and Chorea v0.307 | KCNN2 |
Bryony Thompson gene: KCNN2 was added gene: KCNN2 was added to Dystonia - complex. Sources: Expert Review Green,Literature Mode of inheritance for gene: KCNN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNN2 were set to 32212350; 33242881 Phenotypes for gene: KCNN2 were set to Dystonia 34, myoclonic, MIM#619724; Neurodevelopmental disorder with or without variable movement or behavioural abnormalities, MIM#619725 |
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| Dystonia and Chorea v0.306 | KCNMA1 |
Bryony Thompson gene: KCNMA1 was added gene: KCNMA1 was added to Dystonia - complex. Sources: Expert Review Green,Expert list Mode of inheritance for gene: KCNMA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNMA1 were set to 26195193; 15937479; 29356177 Phenotypes for gene: KCNMA1 were set to Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy MIM#609446 Mode of pathogenicity for gene: KCNMA1 was set to Other |
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| Dystonia and Chorea v0.305 | HPCA |
Bryony Thompson gene: HPCA was added gene: HPCA was added to Dystonia - complex. Sources: Expert Review Green,Royal Melbourne Hospital Mode of inheritance for gene: HPCA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HPCA were set to 25799108; 30991467; 30145809 Phenotypes for gene: HPCA were set to Dystonia 2, torsion, autosomal recessive, 224500; MONDO:0009141; childhood-onset generalized dystonia; adolescence-onset segmental dystonia; generalized dystonia with additional neurological features |
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| Dystonia and Chorea v0.303 | GCH1 |
Bryony Thompson gene: GCH1 was added gene: GCH1 was added to Dystonia - complex. Sources: Expert Review Green,Royal Melbourne Hospital Mode of inheritance for gene: GCH1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: GCH1 were set to 7874165; 11113234; 15753436 Phenotypes for gene: GCH1 were set to Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230 |
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| Dystonia and Chorea v0.302 | GABRB3 |
Bryony Thompson gene: GABRB3 was added gene: GABRB3 was added to Dystonia - complex. Sources: Expert Review Green,Literature Mode of inheritance for gene: GABRB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GABRB3 were set to 37647766 Phenotypes for gene: GABRB3 were set to Developmental and epileptic encephalopathy 43 MIM#617113 Mode of pathogenicity for gene: GABRB3 was set to Other |
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| Dystonia and Chorea v0.301 | DRD2 |
Bryony Thompson gene: DRD2 was added gene: DRD2 was added to Dystonia - complex. Sources: Expert Review Amber,Literature Mode of inheritance for gene: DRD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DRD2 were set to 33200438 Phenotypes for gene: DRD2 were set to Combined dystonia, MONDO:0020065, DRD2-related; dystonia; chorea; anxiety; ataxia; orofacial dyskinesia; tremor; memory problems Penetrance for gene: DRD2 were set to Complete Mode of pathogenicity for gene: DRD2 was set to Other |
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| Dystonia and Chorea v0.298 | CACNA1B |
Bryony Thompson gene: CACNA1B was added gene: CACNA1B was added to Dystonia - complex. Sources: Expert Review Red,Other Mode of inheritance for gene: CACNA1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CACNA1B were set to 25296916; 26157024; 35698023; 33051750; 35041927 Phenotypes for gene: CACNA1B were set to Myoclonus-dystonia syndrome MONDO:0000903 |
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| Dystonia and Chorea v0.292 | ADCY5 |
Bryony Thompson gene: ADCY5 was added gene: ADCY5 was added to Dystonia - complex. Sources: Expert Review Green,Royal Melbourne Hospital Mode of inheritance for gene: ADCY5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ADCY5 were set to 22782511; 24700542; 33051786; 32647899; 33704598; 34631954; 28971144; 30975617 Phenotypes for gene: ADCY5 were set 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 |
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| Dystonia and Chorea v0.286 | MRPS36 |
Krithika Murali gene: MRPS36 was added gene: MRPS36 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: MRPS36 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MRPS36 were set to PMID: 41018056; 38685873 Phenotypes for gene: MRPS36 were set to Leigh syndrome - MONDO:0009723, MRPS36/KGD4-related Review for gene: MRPS36 was set to AMBER Added comment: 3 individuals from 2 unrelated families reported with biallelic MRPS36 variants (current HGNC is KGD4). Gene encodes E4 subunit of OGDHC complex. Individuals present with a phenotype consistent with Leigh syndrome including seizures, hypotonia, dystonia, brain imaging anomalies, persistent lactic acidosis. Cardiomyopathy also reported. Patient-derived fibroblast studies demonstrates reduced OGDHC enzymatic activity, however, this functional evidence is not gene or variant-specific. Sources: Literature |
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| Dystonia and Chorea 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 and Chorea v0.283 | POLR3A | Zornitza Stark Phenotypes for gene: POLR3A were changed from Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 607694; Striatal abnormalities; Dystonia to POLR3A-related disorder MONDO:0700276 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.282 | POLR3A | Zornitza Stark edited their review of gene: POLR3A: Changed phenotypes: POLR3A-related disorder MONDO:0700276 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.281 | PDE1B |
Zornitza Stark gene: PDE1B was added gene: PDE1B was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: PDE1B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDE1B were set to 40492975 Phenotypes for gene: PDE1B were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PDE1B-related Review for gene: PDE1B was set to GREEN Added comment: PMID:40492975 reported seven individuals from five unrelated families identified with biallelic PDE1B variants. Three truncating (p.Gln45Ter, p.Gln86Ter, p.Ser298Alafs*6) and three splicing variants (c.594 + 2 T>G, c.735 + 5G>A, c.837-1G>C) were identified from these patients in total. They presented with an early-onset movement disorder characterised by hypotonia in infancy, progressing to ataxia and dystonia in early childhood, with motor and speech delay, and intellectual disability. Functional evidence is also available for these variants. Sources: Literature |
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| Dystonia and Chorea v0.275 | ARX_EIEE1_GCN2 |
Bryony Thompson STR: ARX_EIEE1_GCN2 was added STR: ARX_EIEE1_GCN2 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for STR: ARX_EIEE1_GCN2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for STR: ARX_EIEE1_GCN2 were set to 11889467; 33811808 Phenotypes for STR: ARX_EIEE1_GCN2 were set to Developmental and epileptic encephalopathy 1 MIM#308350; Intellectual disability, X-linked 29 and others MIM#300419; Partington syndrome MIM#309510 Review for STR: ARX_EIEE1_GCN2 was set to GREEN STR: ARX_EIEE1_GCN2 was marked as clinically relevant STR: ARX_EIEE1_GCN2 was marked as current diagnostic Added comment: NM_139058.3(ARX):c.429GGC[X] Mechanism of disease is polyAlanine tract associated with dominant-negative effect PolyAla tract 2 of 2 polyAla tracts associated with disease Normal repeat number: 12 Pathogenic repeat number: 20 Sources: Expert list |
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| Dystonia and Chorea v0.273 | ARX_EIEE1_GCN1 |
Bryony Thompson STR: ARX_EIEE1_GCN1 was added STR: ARX_EIEE1_GCN1 was added to Dystonia - complex. Sources: Expert Review Mode of inheritance for STR: ARX_EIEE1_GCN1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for STR: ARX_EIEE1_GCN1 were set to 11889467; 33811808 Phenotypes for STR: ARX_EIEE1_GCN1 were set to Developmental and epileptic encephalopathy 1 MIM#308350; Intellectual disability, X-linked 29 and others MIM#300419; Partington syndrome MIM#309510 Review for STR: ARX_EIEE1_GCN1 was set to GREEN STR: ARX_EIEE1_GCN1 was marked as clinically relevant STR: ARX_EIEE1_GCN1 was marked as current diagnostic Added comment: NM_139058.3(ARX):c.306GGC[X] Mechanism of disease is polyAlanine tract associated with dominant-negative effect PolyAla tract 1 of 2 polyAla tracts associated with disease Normal repeat number: 16 Pathogenic repeat number: 23 Sources: Expert Review |
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| Dystonia and Chorea v0.271 | PDGFB |
Sangavi Sivagnanasundram changed review comment from: Disease characterised by calcifications predominantly affecting the basal ganglia of the brain however can affect other areas of the brain as well. Affected individuals report abnormal motor symptoms and psychiatric manifestations. PMID: 36690225 - 24yr with brain calcification and neuropsychiatric symptoms. The affected individual also presented with chorea and dystonia. A novel homozygous Ser305del variant was identified. PMID: 34736156 - three unrelated individuals reported across different articles with brain calcification shown on brain imaging along with paroxysmal dystonia.; to: Disease characterised by calcifications predominantly affecting the basal ganglia of the brain however can affect other areas of the brain as well. Affected individuals report abnormal motor symptoms and psychiatric manifestations. PMID: 36690225 - 24yr with brain calcification and neuropsychiatric symptoms. The affected individual also presented with chorea and dystonia. A novel homozygous Ser305del variant was identified. PMID: 34736156 - three unrelated individuals reported across different publications with brain calcification shown on brain imaging along with paroxysmal dystonia. |
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| Dystonia and Chorea v0.270 | PDGFB | Sangavi Sivagnanasundram reviewed gene: PDGFB: Rating: GREEN; Mode of pathogenicity: None; Publications: 36690225, 34736156; Phenotypes: Primary familial brain calcifications, basal ganglia calcification, idiopathic, 5 MONDO:0014204; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.270 | FTL | Zornitza Stark Phenotypes for gene: FTL were changed from Neurodegeneration with brain iron accumulation 3 606159 to Neurodegeneration with brain iron accumulation 3, MIM# 606159 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.264 | HTRA2 | Zornitza Stark reviewed gene: HTRA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 3-methylglutaconic aciduria type 8 MONDO:0044723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.264 | HTRA2 | Zornitza Stark Phenotypes for gene: HTRA2 were changed from 3-methylglutaconic aciduria, type VIII 617248 to 3-methylglutaconic aciduria type 8 MONDO:0044723 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.262 | NKX6-2 | Zornitza Stark Phenotypes for gene: NKX6-2 were changed from Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy 617560 to Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy MIM#617560 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.256 | PANK2 | Zornitza Stark Phenotypes for gene: PANK2 were changed from pantothenate kinase-associated neurodegeneration; Dystonia to pantothenate kinase-associated neurodegeneration MONDO:0009319; Dystonia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.254 | PANK2 | Sangavi Sivagnanasundram changed review comment from: Established gene-disease association with affected individuals presenting with generalised or lower limb dystonia.; to: Established gene-disease association with affected individuals presenting with generalised or lower limb dystonia along with other psychiatric/behavioural problems. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.254 | PANK2 | Sangavi Sivagnanasundram reviewed gene: PANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15911822; Phenotypes: pantothenate kinase-associated neurodegeneration MONDO:0009319; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.254 | NPC2 | Sangavi Sivagnanasundram reviewed gene: NPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34993563, 17470133; Phenotypes: Niemann-Pick disease, type C2 MONDO:0011873; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.254 | NPC1 | Sangavi Sivagnanasundram reviewed gene: NPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12555942, 20301473; Phenotypes: Niemann-Pick disease, type C1 MONDO:0009757; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.254 | NKX6-2 | Sangavi Sivagnanasundram reviewed gene: NKX6-2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30285346, 28575651, 28969374; Phenotypes: spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy MONDO:0033043; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.254 | HTRA2 | Sangavi Sivagnanasundram reviewed gene: HTRA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27208207, 27696117, 30114719; Phenotypes: 3-methylglutaconic aciduria type 8 MONDO:0044723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.254 | GLB1 | Sangavi Sivagnanasundram reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24156116, 35937492, 34514040, 1353343; Phenotypes: GM1 gangliosidosis type 3 MONDO:0009262; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.254 | GCDH | Sangavi Sivagnanasundram reviewed gene: GCDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 32777384, 21912879, 31536184; Phenotypes: glutaryl-CoA dehydrogenase deficiency MONDO:0009281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.254 | FTL | Sangavi Sivagnanasundram reviewed gene: FTL: Rating: GREEN; Mode of pathogenicity: None; Publications: 11438811, 15099026, 12746423, 18413574; Phenotypes: neuroferritinopathy MONDO:0011638; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.254 | FA2H | Sangavi Sivagnanasundram reviewed gene: FA2H: Rating: GREEN; Mode of pathogenicity: None; Publications: 19068277, 20104589, 20853438, 31135052; Phenotypes: hereditary spastic paraplegia 35 MONDO:0012866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.254 | DLAT | Sangavi Sivagnanasundram reviewed gene: DLAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 39007626, 20022530, 16049940; Phenotypes: pyruvate dehydrogenase E2 deficiency MONDO:0009502; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.249 | C19orf12 | Zornitza Stark Phenotypes for gene: C19orf12 were changed from mitochondrial membrane protein-associated neurodegeneration; neurodegeneration with brain iron accumulation-4; Dystonia to neurodegeneration with brain iron accumulation 4 MONDO:0013674 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.247 | COASY | Zornitza Stark Phenotypes for gene: COASY were changed from COASY protein-associated neurodegeneration; Neurodegeneration with brain iron accumulation 6 615643 to neurodegeneration with brain iron accumulation 6, MONDO:0014290; Neurodegeneration with brain iron accumulation 6 615643 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.242 | DDC | Sangavi Sivagnanasundram reviewed gene: DDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 20505134; Phenotypes: aromatic L-amino acid decarboxylase deficiency MONDO:0012084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.242 | DCAF17 | Sangavi Sivagnanasundram reviewed gene: DCAF17: Rating: GREEN; Mode of pathogenicity: None; Publications: 18175354, 36185913, 17167799; Phenotypes: Woodhouse-Sakati syndrome MONDO:0009419; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.242 | COASY | Sangavi Sivagnanasundram reviewed gene: COASY: Rating: GREEN; Mode of pathogenicity: None; Publications: 23447832, 24360804, 27021474; Phenotypes: neurodegeneration with brain iron accumulation 6 MONDO:0014290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.242 | C19orf12 | Sangavi Sivagnanasundram reviewed gene: C19orf12: Rating: GREEN; Mode of pathogenicity: None; Publications: 21981780, 22508347; Phenotypes: neurodegeneration with brain iron accumulation 4 MONDO:0013674; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.242 | BCAP31 | Sangavi Sivagnanasundram reviewed gene: BCAP31: Rating: GREEN; Mode of pathogenicity: None; Publications: 24011989, 28332767, 30713915, 31330203, 32652807; Phenotypes: severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome MONDO:0010334; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.242 | ATP13A2 | Sangavi Sivagnanasundram reviewed gene: ATP13A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21094623, 20853184, 20310007; Phenotypes: Kufor-Rakeb syndrome MONDO:0011706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea 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 and Chorea v0.240 | KCNQ2 | Bryony Thompson edited their review of gene: KCNQ2: Added comment: Now 2 cases have been reported with dystonic features as part of a complex neurological phenotype.; Changed rating: AMBER; Changed publications: 12742592, 32585800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.240 | APTX | Sangavi Sivagnanasundram reviewed gene: APTX: Rating: GREEN; Mode of pathogenicity: None; Publications: 15876520; Phenotypes: ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia MONDO:0008842; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.240 | ADAR | Sangavi Sivagnanasundram reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301648, 24262145; Phenotypes: Aicardi-Goutieres syndrome MONDO:0018866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.239 | GABRB2 |
Bryony Thompson gene: GABRB2 was added gene: GABRB2 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: GABRB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GABRB2 were set to 38996765 Phenotypes for gene: GABRB2 were set to epileptic encephalopathy, infantile or early childhood, 2 MONDO:0020631 Mode of pathogenicity for gene: GABRB2 was set to Other Review for gene: GABRB2 was set to GREEN gene: GABRB2 was marked as current diagnostic Added comment: At least 7 cases reported with dystonia as a feature of phenotype associated with gain-of-function variants. Sources: Literature |
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| Dystonia and Chorea v0.236 | PNPLA8 |
Chirag Patel gene: PNPLA8 was added gene: PNPLA8 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PNPLA8 were set to PMID: 39082157 Phenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases Review for gene: PNPLA8 was set to GREEN gene: PNPLA8 was marked as current diagnostic Added comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 11/15 individuals (info available) had dystonia (onset in childhood). Using cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development. Sources: Literature |
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| Dystonia and Chorea v0.235 | ACBD6 | Zornitza Stark Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder (MONDO#0700092), ACBD6-related to Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.234 | ACBD6 | Zornitza Stark reviewed gene: ACBD6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.234 | PAH |
Natalie Lim gene: PAH was added gene: PAH was added to Dystonia - complex. Sources: Expert Review Mode of inheritance for gene: PAH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PAH were set to PMID: 25614310, PMID: 15390012, PMID: 30369906 Phenotypes for gene: PAH were set to Phenylketonuria MIM#261600 Review for gene: PAH was set to GREEN Added comment: Reports of parkinsonism and dystonia have been documented as delayed manifestations amongst PKU patients although rare. Sources: Expert Review |
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| Dystonia and Chorea v0.232 | ACBD6 | Elena Savva Gene: acbd6 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.232 | ACBD6 |
Lucy Spencer gene: ACBD6 was added gene: ACBD6 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: ACBD6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACBD6 were set to 37951597 Phenotypes for gene: ACBD6 were set to Neurodevelopmental disorder (MONDO#0700092), ACBD6-related Review for gene: ACBD6 was set to GREEN Added comment: PMID: 37951597 45 individuals from 28 families with a neurodevelopmental syndrome with complex and progressive movement disorder phenotype. 18 PTCs and splice, 1 missense 1 in frame insertion. Phenotypes: weight was >50th percentile in 20/34 patients, all mod-severe GDD, facial dysmorphism in 38/40, mild cerebellar ataxia 35/41, limb spasticity/hypertonia 31/41, gait abnormalities in 33/35, dystonia in 30/31. Sources: Literature |
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| Dystonia and Chorea v0.232 | MAPT | Bryony Thompson edited their review of gene: MAPT: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.231 | ATP2B2 |
Andrew Fennell gene: ATP2B2 was added gene: ATP2B2 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: ATP2B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP2B2 were set to PMID: 37675773 Phenotypes for gene: ATP2B2 were set to Neurodevelopmental Disorder, MONDO:0700092, ATP2B2-related Mode of pathogenicity for gene: ATP2B2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: ATP2B2 was set to GREEN Added comment: 7 unrelated individuals reported with a variable phenotype including dystonia, ataxia, intellectual disability, behavioural symptoms, and seizures. All patients have either missense variants or frameshift variants in the penultimate exon not expected to lead to NMD. This is in contrast to patients with isolated deafness previously reported to have nonsense, frameshift, or splice-site variants outside of this region. Sources: Literature |
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| Dystonia and Chorea v0.229 | SHQ1 | Zornitza Stark edited their review of gene: SHQ1: Added comment: Two more individuals with dystonia reported.; Changed rating: GREEN; Changed publications: 34542157, 29178645, 36847845, 37475611 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.229 | EIF4A2 | Zornitza Stark Phenotypes for gene: EIF4A2 were changed from Neurodevelopmental disorder (MONDO:0700092), EIF4A2-related to Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures, MIM# 620455 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.226 | EIF4A2 | Zornitza Stark edited their review of gene: EIF4A2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.226 | EIF4A2 | Zornitza Stark reviewed gene: EIF4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), EIF4A2-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.224 | TSPOAP1 | Zornitza Stark reviewed gene: TSPOAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia 22, MIM# 620453; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.224 | NUP54 | Zornitza Stark Phenotypes for gene: NUP54 were changed from Striatonigral degeneration, MONDO:0003122, NUP54-related; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia to Dystonia 37, early-onset, with striatal lesions, MIM# 620427; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.222 | SLC30A9 |
Lucy Spencer gene: SLC30A9 was added gene: SLC30A9 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: SLC30A9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC30A9 were set to 37041080 Phenotypes for gene: SLC30A9 were set to Birk-Landau-Perez syndrome (MIM#617595) Review for gene: SLC30A9 was set to GREEN Added comment: PMID:37041080 - 2 families previously reported and this paper describes 4 more with biallelic SLC30A9 variants. Original 2 families: 6 affected members all hom for Ala350del, and 1 affected member chet for 2 frameshifts. 4 families from this paper: 2 families have the same homozygous missense (Gly418Val), family 3 has 4 affected sibs hom for Ala350del, family 4 1 affected chet for a frameshift and a synonymous. So 2 fams homs for Ala350del and 2 fams hom for Gly418Val. All have Brik-Landau-Perez syndrome: all with ID, movement disorder and dystonia, and many with oculomotor apraxia, renal abnormalitie, ptosis, some had hearing impairment. Sources: Literature |
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| Dystonia and Chorea v0.222 | TRPM3 | Zornitza Stark Phenotypes for gene: TRPM3 were changed from Intellectual disability; epilepsy; chorea; athetosis; hypotonia; dysmorphic features to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures, MIM# 620224 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.220 | TRPM3 | Zornitza Stark reviewed gene: TRPM3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures, MIM# 620224; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.220 | TRPM3 |
Shekeeb Mohammad gene: TRPM3 was added gene: TRPM3 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: TRPM3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRPM3 were set to 31278393; 35146895 Phenotypes for gene: TRPM3 were set to Intellectual disability; epilepsy; chorea; athetosis; hypotonia; dysmorphic features Penetrance for gene: TRPM3 were set to Complete Review for gene: TRPM3 was set to GREEN gene: TRPM3 was marked as current diagnostic Added comment: Sources: Literature |
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| Dystonia and Chorea v0.219 | NUP54 |
Zornitza Stark gene: NUP54 was added gene: NUP54 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: NUP54 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP54 were set to 36333996 Phenotypes for gene: NUP54 were set to Striatonigral degeneration, MONDO:0003122, NUP54-related; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia Review for gene: NUP54 was set to AMBER Added comment: From PMID: 36333996.; Harrer, P. et al. (2022) Ann Neurol. doi: 10.1002/ana.26544. Three patients from unrelated families with dystonia and/or Leigh(-like) syndromes, with biallelic variants in NUP54, in the C-terminal protein region that interacts with NUP62. Onset was between 12 months and 5 years. All had progressive neurological deterioration with dystonia, ataxia, dysarthria, dysphagia, hypotonia. Patient / Family A (consanguineous) was homozygous for c.1073T>G p.(Ile358Ser). Patient / Family B was compound heterozygous for c.1073T>G p.(Ile358Ser) and c.1126A>G p.(Lys376Glu). Patient / Family C was compound heterozygosity for c.1410_1412del p.(Gln471del) and two missense variants c.1414G>A, p.(Glu472Lys); c.1420C>T, p.(Leu474Phe) The phenotypes were similar to those of NUP62 including early-onset dystonia with dysphagic choreoathetosis, and T2-hyperintense lesions in striatum. Brain MRIs showed T2/FLAIR hyperintensities in the dorsal putamina. Western blots showing reduced expression of NUP54 and its interaction partners NUP62/NUP58 in patient fibroblasts. Sources: Literature |
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| Dystonia and Chorea v0.215 | AFG3L2 | Shekeeb Mohammad reviewed gene: AFG3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36110148; Phenotypes: dystonia, parkinsonism, intellectual disability, optic hypoplasia, dementia, cognitive decline; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.215 | SHQ1 | Zornitza Stark Phenotypes for gene: SHQ1 were changed from Dystonia; Neurodegeneration to Dystonia 35, childhood-onset , MIM# 619921; Neurodevelopmental disorder with dystonia and seizures, MIM# 619922 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.214 | SHQ1 | Zornitza Stark edited their review of gene: SHQ1: Changed phenotypes: Dystonia 35, childhood-onset , MIM# 619921, Neurodevelopmental disorder with dystonia and seizures, MIM# 619922 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.214 | NR4A2 | Zornitza Stark Phenotypes for gene: NR4A2 were changed from Intellectual Disability; Dystonia and Early-onset Parkinson to Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism, MIM# 619911 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.212 | ZNF526 | Zornitza Stark edited their review of gene: ZNF526: Changed phenotypes: Dentici-Novelli neurodevelopmental syndrome, MIM# 619877 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.212 | FBXO28 | Zornitza Stark Phenotypes for gene: FBXO28 were changed from infantile spasms; developmental epileptic encephalopathy; microcephaly; hypotonia; dystonia; intellectual disability; progressive myoclonic epilepsy to Developmental and epileptic encephalopathy 100, MIM# 619777 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.210 | FBXO28 | Zornitza Stark reviewed gene: FBXO28: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 100, MIM# 619777; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.210 | TNPO2 | Zornitza Stark Phenotypes for gene: TNPO2 were changed from global developmental delay; dysmorphic features; ophthalmologic abnormalities; intellectual disability; fever induced seizures; epilepsy, dystonia; cerebellar dysplasia; cerebllar dysplasia; microcephaly to Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies, MIM# 619556 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.208 | FBXO28 |
Shekeeb Mohammad gene: FBXO28 was added gene: FBXO28 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: FBXO28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FBXO28 were set to 33280099 Phenotypes for gene: FBXO28 were set to infantile spasms; developmental epileptic encephalopathy; microcephaly; hypotonia; dystonia; intellectual disability; progressive myoclonic epilepsy Penetrance for gene: FBXO28 were set to unknown Review for gene: FBXO28 was set to GREEN gene: FBXO28 was marked as current diagnostic Added comment: Sources: Literature |
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| Dystonia and Chorea v0.208 | TNPO2 | Shekeeb Mohammad edited their review of gene: TNPO2: Set current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.208 | TNPO2 |
Shekeeb Mohammad gene: TNPO2 was added gene: TNPO2 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: TNPO2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TNPO2 were set to 34314705 Phenotypes for gene: TNPO2 were set to global developmental delay; dysmorphic features; ophthalmologic abnormalities; intellectual disability; fever induced seizures; epilepsy, dystonia; cerebellar dysplasia; cerebllar dysplasia; microcephaly Penetrance for gene: TNPO2 were set to unknown Review for gene: TNPO2 was set to GREEN Added comment: The movement disorder noted is a complex dystonia, with hyperkinetic components and some patients have episodic exacerbations Sources: Literature |
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| Dystonia and Chorea 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 and Chorea v0.204 | GAMT | Zornitza Stark reviewed gene: GAMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 19027335, 33996490, 12557293, 19288536, 16855203; Phenotypes: Cerebral creatine deficiency syndrome 2 MIM#612736; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.202 | AFG3L2 | Zornitza Stark Mode of inheritance for gene: AFG3L2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.201 | AFG3L2 | Zornitza Stark reviewed gene: AFG3L2: Rating: RED; Mode of pathogenicity: None; Publications: 32219868; Phenotypes: Early-onset dystonia; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.200 | ATP5G3 |
Zornitza Stark gene: ATP5G3 was added gene: ATP5G3 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: ATP5G3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP5G3 were set to 34636445; 34954817 Phenotypes for gene: ATP5G3 were set to Dystonia, early-onset, and/or spastic paraplegia, MIM# 619681 Review for gene: ATP5G3 was set to GREEN Added comment: Note that HGNC approved gene name is ATP5MC3. PMID: 34636445 reports a missense variant identified in a large single-family pedigree with dystonia and spastic paraplegia. The variant was identified via exome sequencing of the proband and a distant cousin, focussing on variants within the previously determined linkage region. The identical missense variant was also identified in a patient with childhood onset dystonic syndrome and was shown to be de novo. Functional studies of fibroblast cell lines from affected father (HSP) and proband of large family demonstrated decreased complex V function. A drosophila model containing the missense variant had reduced mobility and reduced complex V activity. PMID: 34954817 reports de novo monoallelic missense variants in three individuals, however one of these individuals was reported in above paper. The other two patients were: (1) a-15-year-old girl with milestone delay, pyramidal signs, and generalized dystonia with prominent upper-body involvement, and (2) a 6-year-old boy with delayed psychomotor development, lower-extremity spasticity, and elevated blood lactate levels Sources: Literature |
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| Dystonia and Chorea v0.198 | SPATA5L1 | Zornitza Stark Phenotypes for gene: SPATA5L1 were changed from Intellectual disability; spastic-dystonic cerebral palsy; epilepsy; hearing loss to Neurodevelopmental disorder with hearing loss and spasticity, MIM# 619616 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.197 | SPATA5L1 | Zornitza Stark reviewed gene: SPATA5L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hearing loss and spasticity, MIM# 619616; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.196 | SPATA5L1 |
Paul De Fazio gene: SPATA5L1 was added gene: SPATA5L1 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: SPATA5L1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPATA5L1 were set to 34626583 Phenotypes for gene: SPATA5L1 were set to Intellectual disability; spastic-dystonic cerebral palsy; epilepsy; hearing loss Review for gene: SPATA5L1 was set to GREEN gene: SPATA5L1 was marked as current diagnostic Added comment: 47 individuals from 26 unrelated families from various ethnicities with biallelic variants reported. Phenotypes include ID, hearing impairment, movement disorder, abnormal MRI, hypotonia, visual impairment, epilepsy, and microcephaly. Most individuals presented with spasticity (68%), dystonia (60%), or a combination of the two (52%). Sources: Literature |
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| Dystonia and Chorea v0.195 | CHD8 |
Zornitza Stark gene: CHD8 was added gene: CHD8 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: CHD8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CHD8 were set to 34415117 Phenotypes for gene: CHD8 were set to Neurodevelopmental disorder, CHD8-related, MIM#615032; Dystonia Review for gene: CHD8 was set to AMBER Added comment: Two individuals reported with marked childhood-onset dystonia on background of neurodevelopmental issues, phenotype expansion. Sources: Literature |
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| Dystonia and Chorea v0.193 | SHQ1 |
Zornitza Stark gene: SHQ1 was added gene: SHQ1 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: SHQ1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SHQ1 were set to 34542157; 29178645 Phenotypes for gene: SHQ1 were set to Dystonia; Neurodegeneration Review for gene: SHQ1 was set to AMBER Added comment: Three unrelated families reported. Family 1: isolated dystonia only; Family 2: dystonia, and neurodegeneration; Family 3: neurodegeneration. Rated Amber as phenotypes likely represent a continuum but currently unclear what proportion will have complex dystonia. Sources: Literature |
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| Dystonia and Chorea v0.192 | IMPDH2 | Arina Puzriakova reviewed gene: IMPDH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34305140; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.191 | FTDALS |
Bryony Thompson STR: FTDALS was added STR: FTDALS was added to Dystonia - complex. Sources: Expert list Mode of inheritance for STR: FTDALS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: FTDALS were set to 26166205; 24363131; 26187722; 25577942; 21944779; 21944778 Phenotypes for STR: FTDALS were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MIM#105550 Review for STR: FTDALS was set to GREEN STR: FTDALS was marked as clinically relevant Added comment: NG_031977.1:g.5321GGGGCC[X] Repeat expansion affects the protein degradation pathways and may contribute to TDP‐43 accumulation Normal alleles: ≤25 G4C2 hexanucleotide repeat units generally considered normal Pathogenic high-penetrance alleles: ≥60 G4C2 hexanucleotide repeat units are considered pathogenic Note: The minimal size of a G4C2 pathogenic repeat is under debate: some studies consider repeats of >30 G4C2 hexanucleotide repeat units as pathogenic, whereas others use a cutoff of 60 G4C2 hexanucleotide repeat units. Sources: Expert list |
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| Dystonia and Chorea v0.190 | Bryony Thompson removed STR:C9orf72 from the panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.188 | RNU7-1 | Zornitza Stark reviewed gene: RNU7-1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 9, MIM# 619487; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.188 | CAMK4 | Zornitza Stark edited their review of gene: CAMK4: Changed phenotypes: Intellectual disability, Autism, Behavioral abnormality, Abnormality of movement, Dystonia, Ataxia, Chorea, Myoclonus | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.186 | CAMK4 |
Zornitza Stark gene: CAMK4 was added gene: CAMK4 was added to Dystonia - complex. Sources: Expert Review Mode of inheritance for gene: CAMK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CAMK4 were set to 30262571; 33098801; 33211350 Phenotypes for gene: CAMK4 were set to 30262571; 33098801; 33211350 Review for gene: CAMK4 was set to GREEN Added comment: 3 publications by Zech et al (2018, 2020 - PMIDs : 30262571, 33098801, 33211350) provide clinical details on 3 individuals, each harboring a private de novo CAMK4 variant. Overlapping features included DD, ID, behavoral issues, autism and abnormal hyperkinetic movements. Dystonia and chorea in all 3 appeared 3-20 years after initial symptoms. CAMK4 encodes Calcium/Calmodulin-dependent protein kinase IV, an important mediator of calcium-mediated activity and dynamics, particularly in the brain. It is involved in neuronal transmission, synaptic plasticity, and neuronal gene expression required for brain development and neuronal homeostasis (summary by OMIM based on Zech et al, 2018). The 473 aa enzyme has a protein kinase domain (aa 46-300) and a C-terminal autoregulatory domain (aa 305-341) the latter comprising an autoinhibitory domain (AID / aa 305-321) and a calmodulin-binding domain (CBD / aa 322-341) [NP_001735.1 / NM_001744.4 - also used below]. Variants in all 3 subjects were identified following trio-WES and were in all cases protein-truncating, mapping to exon 10 or exon 10-intron 10 junction, expected to escape NMD and cause selective abrogation of the autoinhibitory domain (aa 305-321) leading overall to gain-of-function. Variation databases include pLoF CAMK4 variants albeit in all cases usptream or downstream of this region (pLI of this gene in gnomAD: 0.51). Variants leading to selective abrogation of the autoregulatory domain have not been reported. Extensive evidence for the GoF effect of the variant has been provided in the first publication. Several previous studies have demonstrated that abrogation of the AID domain leads to consitutive activation (details below). Mouse models - though corresponding to homozygous loss of function - support a role for CAMKIV in cognitive and motor symptoms. Null mice display tremulous and ataxic movements, deficiencies in balance and sensorimotor performance associated with reduced number of Purkinje neurons (Ribar et al 2000, PMID: 11069976 - not reviewed). Wei et al (2002, PMID: 12006982 - not reviewed) provided evidence for alteration in hippocampal physiology and memory function. Heterozygous mutations in other genes for calcium/calmodulin-dependent protein kinases (CAMKs) e.g. CAMK2A/CAMK2B (encoding subunits of CAMKII) have been reported in individuals with ID. --- The proband in the first publication (PMID: 30262571) was a male with DD, ID, behavioral difficulties (ASD, autoaggression, stereotypies) and hyperkinetic movement disorder (myoclonus, chorea, ataxia) with severe generalized dystonia (onset at the age of 13y). Brain MRI demonstrated cerebellar atrophy. Extensive work-up incl. karyotyping, CMA, DYT-TOR1A, THAP1, GCH1, SCA1/2/3/6/7/8/12/17, Friedreich's ataxia and FMR1 analysis was negative.F Trio WES identified a dn splice site variant (c.981+1G>A) in the last exon-intron junction. RT-PCR followed by gel electrophoresis and Sanger in fibroblasts from an affected and control subject revealed that the proband had - as predicted by the type/location of the variant - in equal amount 2 cDNA products, a normal as well as a truncated one. Sequencing of the shortest revealed utilization of a cryptic donor splice site upstream of the mutated donor leading to a 77bp out-of-frame deletion and introduction of a premature stop codon in the last codon (p.Lys303Serfs*28). Western blot in fibroblast cell lines revealed 2 bands corresponding to the normal protein product as well as to the p.Lys303Serfs*28 although expression of the latter was lower than that of the full length protein. Several previous studies have shown that mutant CAMKIV species that lack the autoinhibitory domain are consitutively active (several Refs provided). Among others Chatila et al (1996, PMID: 8702940) studied an in vitro-engineered truncation mutant (Δ1-317 - truncation at position 317 of the protein) with functionally validated gain-of-function effect. To prove enhanced activity of the splicing variant, Zech et al assessed phosphorylation of CREB (cyclic AMP-responsive element binding protein), a downstream substrate of CAMKIV. Immunobloting revealed significant increase of CREB phosphorylation in patient fibroblasts compared to controls. Overactivation of CAMKIV signaling was reversed when cells were treated with STO-609 an inhibitor of CAMKK, the ustream activator of CAMKIV. Overall the authors demonstrated that loss of CAMKIV autoregulatory domain due to this splice variant had a gain-of-function effect. ---- Following trio-WES, Zech et al (2020 - PMID: 33098801) identified another relevant subject within cohort of 764 individuals with dystonia. This 12-y.o. male, harboring a different variant affecting the same donor site (c.981+1G>T), presented DD, ID, dystonia (onset at 3y) and additional movement disorders (myoclonus, ataxia) as well as similar behavior (ASD, autoaggression, stereotypies). [Details in suppl. p20]. ---- Finally Zech et al (2020 - PMID: 33211350) reported on a 24-y.o. woman with adolescence onset choreodystonia. Other features included DD, moderate ID, absence seizures in infancy, OCD with anxiety and later diagnosis of ASD. Trio WES revealed a dn stopgain variant (c.940C>T; p.Gln314*). Sources: Expert Review |
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| Dystonia and Chorea v0.185 | IMPDH2 | Zornitza Stark Phenotypes for gene: IMPDH2 were changed from Dystonia to Neurodevelopmental disorder with dystonia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.183 | IMPDH2 |
Laura Raiti gene: IMPDH2 was added gene: IMPDH2 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: IMPDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: IMPDH2 were set to PMID: 33098801 Phenotypes for gene: IMPDH2 were set to Dystonia Review for gene: IMPDH2 was set to GREEN Added comment: 6 unrelated individuals 1x individual in a dystonia cohort index case with infancy-onset dystonia and other neurological manifestations with a de-novo missense variant, c.338G>A (p.Gly113Glu) in IMPDH2, predicted to disrupt an invariant residue within the cystathionine-β-synthase (CBS) domain pair of the encoded protein. IMPDH2 encodes IMPDH2, a key enzyme in the purine biosynthetic pathway, expressed throughout the brain and not linked previously to any human Mendelian condition. 1x individual with a de-novo substitution, c.337G>A (p.Gly113Arg), was found in in-house whole-exome sequencing data from 500 individuals with neurodevelopmental disorders. Through GeneMatcher, de novo variants identified: 3 x missense: c.729G>C (p.Gln243His), c.619G>C (p.Gly207Arg), and c.619G>A (p.Gly207Arg) 1 x deletion: c.478_480delTCC (p.Ser160del) The six variants were predicted to be deleterious and none of them seen in control databases. All affected conserved amino acids and resided in and around the cystathionine-β-synthase domain pair. The described variants are situated in and around the CBS domain pair, a regulatory element in which clustering of pathogenic missense variants has already been shown for the homologue of IMPDH2, IMPDH1. The variant carriers shared similar neurodevelopmental phenotypes. Apart from the dystonia cohort index case, one participant had evidence of dystonic posturing. Modelling of the variants on 3D protein structures revealed spatial clustering near specific functional sites, predicted to result in deregulation of IMPDH2 activity. Additionally, thermal-shift assays showed that the c.619G>A (p.Gly207Arg) variant, identified as within the CBS domain pair, and c.729G>C (p.Gln243His), which is in close vicinity, affected the stability or folding behaviour of IMPDH2. Sources: Literature |
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| Dystonia and Chorea v0.183 | VPS41 | Zornitza Stark Phenotypes for gene: VPS41 were changed from Dystonia; intellectual disability to Spinocerebellar ataxia-29 (SCAR29), MIM#619389; Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.182 | VPS41 | Zornitza Stark edited their review of gene: VPS41: Changed phenotypes: Spinocerebellar ataxia-29 (SCAR29), MIM#619389, Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.180 | EIF2AK2 | Zornitza Stark edited their review of gene: EIF2AK2: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.180 | EIF2AK2 | Zornitza Stark edited their review of gene: EIF2AK2: Added comment: PMID 33866603: further report of dystonia in a 3-generation family, same variant (p.Gly130Arg); Changed publications: 33236446, 33866603 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.180 | UBTF | Zornitza Stark Phenotypes for gene: UBTF were changed from Neurodegeneration, childhood-onset, with brain atrophy MIM#617672 to Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672; MONDO:0044701 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.179 | UBTF | Zornitza Stark reviewed gene: UBTF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672, MONDO:0044701; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea 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 and Chorea v0.176 | VPS16 | Zornitza Stark edited their review of gene: VPS16: Changed phenotypes: Dystonia 30, MIM#619291 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.175 | COQ8A |
Zornitza Stark gene: COQ8A was added gene: COQ8A was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: COQ8A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COQ8A were set to 32337771 Phenotypes for gene: COQ8A were set to Coenzyme Q10 deficiency, primary, 4, MIM# 612016 Review for gene: COQ8A was set to GREEN Added comment: PMID 32337771: cohort of 59 individuals. COQ8A-ataxia presented as variable multisystemic, early-onset cerebellar ataxia, with complicating features ranging from epilepsy (32%) and cognitive impairment (49%) to exercise intolerance (25%) and hyperkinetic movement disorders (41%), including dystonia and myoclonus as presenting symptoms. Sources: Expert list |
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| Dystonia and Chorea v0.174 | MECR | Zornitza Stark Phenotypes for gene: MECR were changed from Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, MIM#617282 to Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, MIM# 617282; MONDO:0015003 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.172 | MECR | Zornitza Stark reviewed gene: MECR: Rating: GREEN; Mode of pathogenicity: None; Publications: 27817865, 33401012, 31137067, 31070877; Phenotypes: Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, MIM# 617282, MONDO:0015003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.171 | VPS4A | Zornitza Stark reviewed gene: VPS4A: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: CIMDAG syndrome MIM# 619273; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.171 | MED27 | Zornitza Stark reviewed gene: MED27: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia, MIM# 619286; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.167 | NR4A2 |
Sebastian Lunke gene: NR4A2 was added gene: NR4A2 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: NR4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: NR4A2 were set to 31922365 Phenotypes for gene: NR4A2 were set to Intellectual Disability; Dystonia and Early-onset Parkinson Review for gene: NR4A2 was set to GREEN Added comment: Three patients described to expand the known phenotype of mild ID with early adulthood onset Dystonia and Early-onset Parkinson. Three patients described in two publications, two with frameshift and one with missense, all de-novo. https://doi.org/10.1212/NXG.0000000000000543 https://doi.org/10.1002/mds.27982 Sources: Literature |
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| Dystonia and Chorea v0.165 | KIF1A |
Bryony Thompson gene: KIF1A was added gene: KIF1A was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: KIF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KIF1A were set to 32096284; 32935419 Phenotypes for gene: KIF1A were set to Dystonia; spastic paraplegia; intellectual disability Review for gene: KIF1A was set to GREEN gene: KIF1A was marked as current diagnostic Added comment: Dystonia was a feature of the phenotype in 4/10 cases with de novo or parental germline mosaic variants. Sources: Literature |
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| Dystonia and Chorea v0.162 | ZNF526 |
Zornitza Stark gene: ZNF526 was added gene: ZNF526 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: ZNF526 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZNF526 were set to 21937992; 25558065; 33397746 Phenotypes for gene: ZNF526 were set to Intellectual disability; Microcephaly; Cataracts; Epilepsy; Hypertonia; Dystonia Review for gene: ZNF526 was set to GREEN Added comment: - PMID: 21937992 (2011) - Two unrelated families (with 4 affected individuals in each) with non-syndromic ID (mild or moderate, respectively) identified harbouring different biallelic missense variants in the ZNF526 gene. - PMID: 25558065 (2015) - One family with ID, Noonan-like facies, pulmonary stenosis and a homozygous missense variant in this gene. No further details provided. - PMID: 33397746 (2021) - Five individuals from four unrelated families with homozygous ZNF526 variants. Four harboured truncating variants, and were all affected by profound DD and severe ID, microcephaly (ranging from -4 SD to -8 SD), bilateral progressive cataracts, hypertonic-dystonic movements, epilepsy and brain MRI anomalies. The fifth patient had a homozygous missense variant and a slightly less severe disorder, with postnatal microcephaly (-2 SD), progressive bilateral cataracts, severe ID, and normal brain MRI. Zebrafish model demonstrated brain and eye malformations resembling findings seen in the human holoprosencephaly spectrum Sources: Literature |
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| Dystonia and Chorea v0.160 | EIF2AK2 |
Zornitza Stark gene: EIF2AK2 was added gene: EIF2AK2 was added to Dystonia - complex. Sources: Expert Review Mode of inheritance for gene: EIF2AK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EIF2AK2 were set to 33236446 Phenotypes for gene: EIF2AK2 were set to Intellectual disability; white matter abnormalities; ataxia; regression with febrile illness; early onset dystonia Review for gene: EIF2AK2 was set to AMBER Added comment: 10 individuals reported with complex neurological phenotype including ataxia and spasticity. Additional report in PMID 33236446 of same missense variant, p.Gly130Arg segregating with disease in 5 individuals from one family, and occurring de novo in another individual with prominent, early-onset dystonia. One more individual identified with a homozygous variant and dystonia. Some functional data to support variant pathogenicity. Three of the individuals had additional neurological features including ID. Sources: Expert Review |
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| Dystonia and Chorea v0.158 | YIF1B | Zornitza Stark Phenotypes for gene: YIF1B were changed from Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement to Kaya-Barakat-Masson syndrome, MIM# 619125; Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.157 | YIF1B | Zornitza Stark edited their review of gene: YIF1B: Changed phenotypes: Kaya-Barakat-Masson syndrome, MIM# 619125, Central hypotonia, Failure to thrive, Microcephaly, Global developmental delay, Intellectual disability, Seizures, Spasticity, Abnormality of movement | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.157 | VPS4A | Elena Savva Deleted their review | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.157 | VPS4A |
Elena Savva Added comment: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life." |
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| Dystonia and Chorea v0.157 | VPS4A | Elena Savva Added comment: Comment on mode of pathogenicity: Dominant negative | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.157 | VPS4A | Elena Savva Mode of pathogenicity for gene: VPS4A was changed from None to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.155 | VPS4A |
Kristin Rigbye gene: VPS4A was added gene: VPS4A was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: VPS4A were set to 33186543; 33186545 Phenotypes for gene: VPS4A were set to Neurodevelopmental disorder Review for gene: VPS4A was set to GREEN Added comment: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life." Sources: Literature |
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| Dystonia and Chorea v0.155 | MOGS |
Zornitza Stark gene: MOGS was added gene: MOGS was added to Dystonia - complex. Sources: Expert Review Mode of inheritance for gene: MOGS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MOGS were set to 33058492 Phenotypes for gene: MOGS were set to Congenital disorder of glycosylation, type IIb, MIM# 606056 Review for gene: MOGS was set to RED Added comment: 7 individuals from 6 unrelated families reported with CDGIIb. Of these, one had prominent dystonia, with forced posture of the head and of both hands, as well as a hyperkinetic movement disorder. Sources: Expert Review |
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| Dystonia and Chorea v0.154 | UNC80 | Zornitza Stark Phenotypes for gene: UNC80 were changed from hypotonia; severe intellectual disability; dyskinesia; dysmorphism to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; MONDO:0014777 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.153 | UNC80 | Zornitza Stark reviewed gene: UNC80: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801, MONDO:0014777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.152 | ALK |
Dean Phelan gene: ALK was added gene: ALK was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: ALK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ALK were set to PMID: 32989326 Phenotypes for gene: ALK were set to Spastic-dystonic diplegia Review for gene: ALK was set to AMBER Added comment: PMID: 32989326 - Large cohort study of cerebral palsy cases identified two de novo variants in two patients with spastic diplegia with mild tremor, scattered subcortical hyperintensities and an atrial septal defect; and spastic-dystonic diplegia, white matter abnormalities and epilepsy, respectively, with no evidence of neuroblastoma in either patient Sources: Literature |
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| Dystonia and Chorea v0.152 | C9orf72 | Bryony Thompson Gene: c9orf72 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.150 | C9orf72 |
Bryony Thompson STR: C9orf72 was added STR: C9orf72 was added to Dystonia - complex. Sources: Expert list STR tags were added to STR: C9orf72. Mode of inheritance for STR: C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: C9orf72 were set to 26166205; 24363131; 26187722; 25577942 Phenotypes for STR: C9orf72 were set to Dystonia; Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MIM#105550 Review for STR: C9orf72 was set to GREEN STR: C9orf72 was marked as clinically relevant Added comment: NG_031977.1:g.5321GGGGCC[X] Repeat expansion affects the protein degradation pathways and may contribute to TDP‐43 accumulation Normal alleles: ≤25 G4C2 hexanucleotide repeat units generally considered normal Pathogenic high-penetrance alleles: ≥60 G4C2 hexanucleotide repeat units are considered pathogenic Note: The minimal size of a G4C2 pathogenic repeat is under debate: some studies consider repeats of >30 G4C2 hexanucleotide repeat units as pathogenic, whereas others use a cutoff of 60 G4C2 hexanucleotide repeat units. Sources: Expert list |
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| Dystonia and Chorea v0.149 | VPS41 |
Zornitza Stark gene: VPS41 was added gene: VPS41 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: VPS41 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS41 were set to 32808683 Phenotypes for gene: VPS41 were set to Dystonia; intellectual disability Review for gene: VPS41 was set to RED Added comment: Single individual reported with homozygous canonical splice site variant resulting in exon 7 skipping, and global developmental delay and generalized dystonia. He attained a few words and voluntary limb movements but never sat unsupported. He had pale optic discs and an axonal neuropathy. From 6 years of age, his condition began to deteriorate, with reduced motor abilities and alertness. An MRI of the brain showed atrophy of the superior cerebellar vermis and slimming of the posterior limb of the corpus callosum. VPS41 is component of the HOPS complex and other genes in the complex have been implicated in movement disorders. Sources: Literature |
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| Dystonia and Chorea v0.147 | VPS16 |
Zornitza Stark gene: VPS16 was added gene: VPS16 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: VPS16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: VPS16 were set to 32808683 Phenotypes for gene: VPS16 were set to Dystonia Review for gene: VPS16 was set to GREEN Added comment: 18 individuals reported with high-impact variants in VPS16 and a progressive early onset dystonia (median age 12 years, range 3–50 years), with prominent oromandibular, bulbar, cervical, and upper limb involvement. Progressive generalization ensued, although most remained ambulant, and only a minority (16%) lost the ability to walk in adulthood. Additional clinical features of mild to moderate intellectual disability and neuropsychiatric symptoms were present in approximately one‐third. In 4 individuals, magnetic resonance imaging (MRI) showed bilateral and symmetrical hypointensity of the globi pallidi and sometimes also the midbrain and dentate nuclei, suggestive of iron deposition. Mild generalized cerebral atrophy was also apparent in 4 individuals. Sources: Literature |
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| Dystonia and Chorea v0.145 | YIF1B |
Zornitza Stark gene: YIF1B was added gene: YIF1B was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: YIF1B were set to 32006098; 26077767 Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement Review for gene: YIF1B was set to GREEN Added comment: 6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function. Sources: Literature |
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| Dystonia and Chorea v0.144 | RHOBTB2 | Zornitza Stark Phenotypes for gene: RHOBTB2 were changed from Dystonia, hypertonia, movement disorder; truncal hypotonia; hemiparesis; developmental and epileptic encephalopathy to Epileptic encephalopathy, early infantile, 64, MIM# 618004; Dystonia, hypertonia, movement disorder; truncal hypotonia; hemiparesis; developmental and epileptic encephalopathy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.142 | RHOBTB2 |
Eunice Chan gene: RHOBTB2 was added gene: RHOBTB2 was added to Dystonia - complex. Sources: Other Mode of inheritance for gene: RHOBTB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RHOBTB2 were set to PMID: 29276004 Phenotypes for gene: RHOBTB2 were set to Dystonia, hypertonia, movement disorder; truncal hypotonia; hemiparesis; developmental and epileptic encephalopathy Added comment: 8/10 patients described had dystonic, paroxysmal, or chorea-like movements Sources: Other |
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| Dystonia and Chorea v0.141 | VAMP1 | Zornitza Stark edited their review of gene: VAMP1: Added comment: Single variant reported in four Newfoundland families, founder effect.; Changed rating: AMBER; Changed phenotypes: Spastic ataxia 1, autosomal dominant, MIM# 108600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.138 | ATP7B | Zornitza Stark reviewed gene: ATP7B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32662046; Phenotypes: Wilson disease, MIM# 277900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.137 | VPS13D |
Zornitza Stark gene: VPS13D was added gene: VPS13D was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: VPS13D was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS13D were set to 29604224; 29518281 Phenotypes for gene: VPS13D were set to Spinocerebellar ataxia, autosomal recessive 4, MIM# 607317 Review for gene: VPS13D was set to GREEN Added comment: 7 unrelated families reported and a mouse model. Most affected individuals have ataxic gait with spasticity and hyperreflexia of the lower limbs resulting in difficulty walking. The age at onset is highly variable: some have onset in early childhood with delayed walking, whereas others have onset of gait difficulties in adulthood. Additional features may include dysarthria, oculomotor abnormalities, distal sensory impairment, dystonia, chorea, hypotonia, pyramidal signs, and cerebellar atrophy on brain imaging. The disorder is slowly progressive. Some individuals with onset in childhood may have global developmental delay with mild intellectual disability. Sources: Expert list |
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| Dystonia and Chorea v0.135 | VAMP2 |
Zornitza Stark gene: VAMP2 was added gene: VAMP2 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: VAMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: VAMP2 were set to 30929742 Phenotypes for gene: VAMP2 were set to Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements 618760; Dystonia; Cortical visual impairment; Seizures; Stereotypic behaviour; Generalized hypotonia; Intellectual disability Review for gene: VAMP2 was set to GREEN Added comment: 5 unrelated patients with heterozygous de novo mutations in VAMP2, presenting with a neurodevelopmental disorder characterized by axial hypotonia, intellectual disability, and autistic features. Affected individuals carrying de novo non-synonymous variants involving the C-terminal region presented a more severe phenotype with additional neurological features, including central visual impairment, hyperkinetic movement disorder, and epilepsy or electroencephalography abnormalities. Reconstituted fusion involving a lipid-mixing assay indicated impairment in vesicle fusion as one of the possible associated disease mechanisms. The abnormal movements included dystonia. Sources: Expert list |
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| Dystonia and Chorea v0.133 | VAMP1 |
Zornitza Stark gene: VAMP1 was added gene: VAMP1 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: VAMP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: VAMP1 were set to 22958904 Phenotypes for gene: VAMP1 were set to Spastic ataxia 1, autosomal dominant, MIM# 108600 Review for gene: VAMP1 was set to GREEN Added comment: Autosomal dominant neurodegenerative disorder characterised by lower-limb spasticity and generalized ataxia with dysarthria, impaired ocular movements, and gait disturbance. Onset is between the ages of 10 and 20 years. Other clinical features are supranuclear gaze palsy, hyperreflexia, hypertonicity, dystonia, pes cavus, mild ptosis, and decreased vibration sense in the lower limbs. Sources: Expert list |
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| Dystonia and Chorea v0.131 | SURF1 |
Zornitza Stark gene: SURF1 was added gene: SURF1 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: SURF1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SURF1 were set to 19780766 Phenotypes for gene: SURF1 were set to Leigh syndrome, due to COX IV deficiency, MIM# 256000 Review for gene: SURF1 was set to GREEN Added comment: SURF1 gene mutations are the most common cause of Leigh syndrome (LS), a progressive neurodegenerative disorder of infancy, characterised by symmetric necrotizing lesions and hypervascularity in the brainstem and basal ganglia. Dystonia is part of the phenotype, particularly in those with milder phenotypes/missense variants. Sources: Expert list |
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| Dystonia and Chorea v0.130 | SQSTM1 | Zornitza Stark Phenotypes for gene: SQSTM1 were changed from Myopathy, distal, with rimmed vacuoles 617158 to Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, MIM# 617145 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.129 | SQSTM1 | Zornitza Stark reviewed gene: SQSTM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, MIM# 617145; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.128 | SLC20A2 | Zornitza Stark reviewed gene: SLC20A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22327515, 23334463, 24411498; Phenotypes: Basal ganglia calcification, idiopathic, 1, MIM# 213600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.128 | SLC16A2 |
Zornitza Stark changed review comment from: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked condition characterized by severely impaired intellectual development, dysarthria, athetoid movements, muscle hypoplasia, and spastic paraplegia. There is large phenotypic interfamilial and intrafamilial variability. Paroxysmal dystonic dyskinesia triggered by passive movements, excitement, crying reported. Sources: Expert Review; to: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked condition characterized by severely impaired intellectual development, dysarthria, athetoid movements, muscle hypoplasia, and spastic paraplegia. There is large phenotypic interfamilial and intrafamilial variability. In a recent review of 24 affected individuals (PMID 31410843), 16 presented with profound developmental delay, three had severe intellectual disability with poor language and walking with an aid, four had moderate intellectual disability with language and walking abilities, and one had mild intellectual disability with hypotonia. Overall, eight had learned to walk, all had hypotonia, 17 had spasticity, 18 had dystonia, 12 had choreoathetosis, 19 had hypomyelination, and 10 had brain atrophy. Kyphoscoliosis (n=12), seizures (n=7), and pneumopathies (n=5) were the most severe complications. Paroxysmal dystonic dyskinesia triggered by passive movements, excitement, crying is reported. Sources: Expert Review |
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| Dystonia and Chorea v0.127 | SLC16A2 |
Zornitza Stark gene: SLC16A2 was added gene: SLC16A2 was added to Dystonia - complex. Sources: Expert Review Mode of inheritance for gene: SLC16A2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: SLC16A2 were set to 15980113; 31410843; 20301789 Phenotypes for gene: SLC16A2 were set to Allan-Herndon-Dudley syndrome, MIM# 300523 Review for gene: SLC16A2 was set to GREEN Added comment: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked condition characterized by severely impaired intellectual development, dysarthria, athetoid movements, muscle hypoplasia, and spastic paraplegia. There is large phenotypic interfamilial and intrafamilial variability. Paroxysmal dystonic dyskinesia triggered by passive movements, excitement, crying reported. Sources: Expert Review |
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| Dystonia and Chorea v0.126 | OPA3 | Zornitza Stark Phenotypes for gene: OPA3 were changed from developmental delay, hypotonia; dystonia and chorea; ataxia, optic atrophy; spastic paraplegia to 3-methylglutaconic aciduria, type III, MIM# 258501; developmental delay, hypotonia; dystonia and chorea; ataxia, optic atrophy; spastic paraplegia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.123 | OPA3 | Zornitza Stark reviewed gene: OPA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 7510656, 2494568, 11668429; Phenotypes: 3-methylglutaconic aciduria, type III, MIM# 258501; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.122 | SETX |
Zornitza Stark gene: SETX was added gene: SETX was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: SETX was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SETX were set to 19696032 Phenotypes for gene: SETX were set to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2, MIM# 606002 Review for gene: SETX was set to GREEN Added comment: Dystonia was present in around 13% in a cohort of 90 affected individuals. Sources: Expert list |
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| Dystonia and Chorea v0.119 | PSEN1 | Zornitza Stark changed review comment from: Variants in this gene are typically associated with Alzheimer's disease and other dementias. One case report of a primary presentation with Parkinsonism-dystonia, later complicated by dementia.; to: Variants in this gene are typically associated with Alzheimer's disease and other dementias but there are reports of complex movement disorders preceding or as part of dementia presentations. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.119 | PSEN1 | Zornitza Stark edited their review of gene: PSEN1: Changed rating: GREEN; Changed publications: 12810495, 15159497, 29316780, 28664294 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.118 | PSEN1 | Zornitza Stark reviewed gene: PSEN1: Rating: RED; Mode of pathogenicity: None; Publications: 28664294; Phenotypes: Dementia, frontotemporal, MIM# 600274; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.117 | POLR3A |
Zornitza Stark gene: POLR3A was added gene: POLR3A was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POLR3A were set to 32600288; 32373668; 31940116; 31932101; 29618326 Phenotypes for gene: POLR3A were set to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 607694; Striatal abnormalities; Dystonia Review for gene: POLR3A was set to GREEN Added comment: Multiple individuals reported where dystonia is part of the phenotype. Some of these have had hypomyelinating leukodystrophy, whereas others have had very prominent striatal abnormalities on MRI, in the absence of white matter changes. It is unclear whether this represents a continuum or a separate disorder. Sources: Expert list |
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| Dystonia and Chorea v0.115 | PNKP |
Zornitza Stark gene: PNKP was added gene: PNKP was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: PNKP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PNKP were set to 28552035; 25728773 Phenotypes for gene: PNKP were set to Ataxia-oculomotor apraxia 4, MIM# 616267 Review for gene: PNKP was set to GREEN Added comment: Dystonia is part of this complex neurological phenotype, which also includes ataxia, oculomotor apraxia and peripheral neuropathy. Sources: Expert list |
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| Dystonia and Chorea v0.114 | PDGFRB | Zornitza Stark Phenotypes for gene: PDGFRB were changed from Dystonia; Basal ganglia calcification, idiopathic, 4 615007 to Basal ganglia calcification, idiopathic, 4, MIM# 615007 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.111 | PDGFRB | Zornitza Stark reviewed gene: PDGFRB: Rating: RED; Mode of pathogenicity: None; Publications: 24518837; Phenotypes: Basal ganglia calcification, idiopathic, MIM#4 615007; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.110 | PCCB |
Zornitza Stark gene: PCCB was added gene: PCCB was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: PCCB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PCCB were set to 30879957 Phenotypes for gene: PCCB were set to Propionicacidemia, MIM# 606054 Review for gene: PCCB was set to GREEN Added comment: The neonatal form is frequently accompanied by metabolic acidosis with anion gap, ketonuria, hypoglycemia, hyperammonemia, and cytopenia. A late-onset form in older children and adults is pertinent to this panel as it has a milder phenotype. It is less common, and may present with developmental regression, chronic vomiting, protein intolerance, failure to thrive, hypotonia, and occasionally basal ganglia infarction, which may result in dystonia and choreoathetosis, and cardiomyopathy. Sources: Expert list |
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| Dystonia and Chorea v0.108 | PCCA |
Zornitza Stark gene: PCCA was added gene: PCCA was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: PCCA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PCCA were set to 30879957 Phenotypes for gene: PCCA were set to Propionicacidemia, MIM# 606054 Review for gene: PCCA was set to GREEN Added comment: The neonatal form is frequently accompanied by metabolic acidosis with anion gap, ketonuria, hypoglycemia, hyperammonemia, and cytopenia. A late-onset form in older children and adults is pertinent to this panel as it has a milder phenotype. It is less common, and may present with developmental regression, chronic vomiting, protein intolerance, failure to thrive, hypotonia, and occasionally basal ganglia infarction, which may result in dystonia and choreoathetosis, and cardiomyopathy. Sources: Expert list |
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| Dystonia and Chorea v0.106 | KIF1C |
Zornitza Stark gene: KIF1C was added gene: KIF1C was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: KIF1C was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF1C were set to 31413903 Phenotypes for gene: KIF1C were set to Spastic ataxia 2, autosomal recessive, MIM# 611302 Review for gene: KIF1C was set to AMBER Added comment: Neurologic disorder characterized by onset in the first 2 decades of cerebellar ataxia, dysarthria, and variable spasticity of the lower limbs. At least one report of a more complex movement disorder including dystonia. Sources: Expert list |
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| Dystonia and Chorea v0.105 | ACTB | Zornitza Stark Mode of pathogenicity for gene: ACTB was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.103 | GNAO1 | Zornitza Stark Mode of pathogenicity for gene: GNAO1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.100 | HPRT1 | Zornitza Stark reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301328; Phenotypes: Lesch-Nyhan syndrome, MIM# 300322; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.99 | HIBCH |
Zornitza Stark gene: HIBCH was added gene: HIBCH was added to Dystonia - complex. Sources: Expert Review Mode of inheritance for gene: HIBCH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HIBCH were set to 26026795; 25251209; 24299452; 32677093 Phenotypes for gene: HIBCH were set to 3-hydroxyisobutryl-CoA hydrolase deficiency, MIM# 250620 Review for gene: HIBCH was set to GREEN Added comment: Autosomal recessive inborn error of metabolism characterized by severely delayed psychomotor development, neurodegeneration, increased lactic acid, and brain lesions in the basal ganglia. Dystonia is a feature. Sources: Expert Review |
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| Dystonia and Chorea v0.97 | ECHS1 |
Zornitza Stark gene: ECHS1 was added gene: ECHS1 was added to Dystonia - complex. Sources: Expert Review Mode of inheritance for gene: ECHS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ECHS1 were set to 32677093; 32858208 Phenotypes for gene: ECHS1 were set to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, MIM# 616277 Review for gene: ECHS1 was set to GREEN Added comment: Paroxysmal and non-paroxysmal dystonia described as a manifestation of this metabolic disorder. Sources: Expert Review |
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| Dystonia and Chorea v0.95 | GTPBP2 |
Zornitza Stark gene: GTPBP2 was added gene: GTPBP2 was added to Dystonia - complex. Sources: Expert Review Mode of inheritance for gene: GTPBP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GTPBP2 were set to 26675814; 29449720; 30790272 Phenotypes for gene: GTPBP2 were set to Jaberi-Elahi syndrome, MIM#617988 Review for gene: GTPBP2 was set to GREEN Added comment: Nine individuals from six unrelated families with bi-allelic variants in this gene causing a neuro-ectodermal syndrome. Key features include prenatal onset microcephaly, tone abnormalities, and movement disorders, epilepsy, dysmorphic features, retinal dysfunction, ectodermal dysplasia, and brain iron accumulation. Sources: Expert Review |
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| Dystonia and Chorea v0.92 | GNB1 | Zornitza Stark edited their review of gene: GNB1: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.92 | GNB1 | Zornitza Stark reviewed gene: GNB1: Rating: RED; Mode of pathogenicity: None; Publications: 27108799, 30194818, 27668284, 31034681; Phenotypes: Mental retardation, autosomal dominant 42, MIM# 616973; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.91 | GJC2 |
Zornitza Stark gene: GJC2 was added gene: GJC2 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: GJC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GJC2 were set to 15192806; 18094336 Phenotypes for gene: GJC2 were set to Leukodystrophy, hypomyelinating, 2, MIM# 608804 Review for gene: GJC2 was set to GREEN Added comment: Complex CNS involvement manifesting as nystagmus, impaired motor development, ataxia, choreoathetotic movements, dystonia, dysarthria, and progressive spasticity, in addition to intellectual disability. Multiple families reported. Sources: Expert list |
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| Dystonia and Chorea v0.87 | FOXG1 | Zornitza Stark reviewed gene: FOXG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27029630; Phenotypes: Rett syndrome, congenital variant, MIM# 613454; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.87 | CYP27A1 | Zornitza Stark Phenotypes for gene: CYP27A1 were changed from Cholestanol storage disease; Dystonia to Cerebrotendinous xanthomatosis, MIM# 213700; Cholestanol storage disease; Dystonia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.85 | CYP27A1 | Zornitza Stark edited their review of gene: CYP27A1: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.85 | CYP27A1 | Zornitza Stark reviewed gene: CYP27A1: Rating: ; Mode of pathogenicity: None; Publications: 19373932, 21531161, 25424010; Phenotypes: Cerebrotendinous xanthomatosis, MIM# 213700; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.84 | CP | Zornitza Stark commented on gene: CP: Iron deposition in brain, specifically in basal ganglia, resulting in extrapyramidal movement disorders as part of the neurodegenerative phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.82 | CACNA1G |
Zornitza Stark changed review comment from: Variable spasticity, hypertonia, or dystonia of the limbs in addition to intellectual disability and ataxia. Sources: Expert list; to: Four unrelated individuals reported with variable spasticity, hypertonia, or dystonia of the limbs in addition to intellectual disability and ataxia. Sources: Expert list |
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| Dystonia and Chorea v0.81 | CACNA1G |
Zornitza Stark gene: CACNA1G was added gene: CACNA1G was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: CACNA1G was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CACNA1G were set to 29878067 Phenotypes for gene: CACNA1G were set to Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits, MIM# 618087 Review for gene: CACNA1G was set to GREEN Added comment: Variable spasticity, hypertonia, or dystonia of the limbs in addition to intellectual disability and ataxia. Sources: Expert list |
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| Dystonia and Chorea v0.79 | C9orf72 |
Zornitza Stark gene: C9orf72 was added gene: C9orf72 was added to Dystonia - complex. Sources: Expert list STR tags were added to gene: C9orf72. Mode of inheritance for gene: C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: C9orf72 were set to 26166205; 24363131; 26187722 Phenotypes for gene: C9orf72 were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, MIM# 105550 Review for gene: C9orf72 was set to GREEN Added comment: Dystonia is a well described feature of this condition. Note condition is caused by heterozygous hexanucleotide repeat expansion (GGGGCC) in a noncoding region of the C9ORF72 gene. Sources: Expert list |
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| Dystonia and Chorea v0.78 | AUH | Zornitza Stark reviewed gene: AUH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 3-methylglutaconic aciduria, type I, MIM# 250950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.77 | ARX | Zornitza Stark edited their review of gene: ARX: Changed publications: 11889467, 15200506 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.77 | ARX | Zornitza Stark Mode of pathogenicity for gene: ARX was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.76 | ARX | Zornitza Stark Phenotypes for gene: ARX were changed from Early infantile epileptic encephalopathy; Dystonia to Partington syndrome, MIM# 309510; Dystonia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.75 | ARX | Zornitza Stark reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Partington syndrome, MIM# 309510; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.75 | TIMM8A | Zornitza Stark Phenotypes for gene: TIMM8A were changed from Deafness-Dystonia-Optic Neuronopathy Syndrome to Deafness-Dystonia-Optic Neuronopathy Syndrome; Mohr-Tranebjaerg syndrome, MIM# 304700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.72 | TIMM8A | Zornitza Stark reviewed gene: TIMM8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 11803487, 11405816, 32820032; Phenotypes: Mohr-Tranebjaerg syndrome, MIM# 304700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.71 | GRIN1 |
Zornitza Stark gene: GRIN1 was added gene: GRIN1 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: GRIN1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: GRIN1 were set to 29365063; 27164704; 27164704; 28051072 Phenotypes for gene: GRIN1 were set to Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, MIM# 614254; Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive, MIM# 617820 Review for gene: GRIN1 was set to GREEN Added comment: Over 20 individuals reported with de novo missense variants in GRIN1 and severe neurodevelopmental phenotype, comprising ID, seizures, and a movement disorder, in particular dystonia. Two families reported with bi-allelic variants: different mechanism postulated (LOF vs affecting channel functioning or hypomorphic alleles), parents were carriers and unaffected. Movement disorder, in particular dystonia also reported in bi-allelic cases. Sources: Expert list |
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| Dystonia and Chorea v0.69 | IRF2BPL |
Elena Savva gene: IRF2BPL was added gene: IRF2BPL was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: IRF2BPL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: IRF2BPL were set to PMID: 30057031; 30166628 Phenotypes for gene: IRF2BPL were set to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures 618088 Review for gene: IRF2BPL was set to GREEN Added comment: PMID: 30057031 - 7 patients with neurodevelopmental regression (5/7), progressive ataxia (5/7), seizures (7/7), spasticity (2/7), dystonia (3/7) and global devel delay (7/7). PTCs produced a more severe phenotype than missense. Onset was in childhood. Cerebellar changes also less frequently reported. PMID: 30166628 - 11 patients with de novo PTCs with childhood neurological regression, epilepsy (7/11), hypotonia (5/11), dystonia (3/11), cerebellar atrophy (5/10). MRI showed CNS defects in 6/10 patients. Sources: Literature |
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| Dystonia and Chorea v0.68 | SQSTM1 |
Elena Savva gene: SQSTM1 was added gene: SQSTM1 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: SQSTM1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SQSTM1 were set to PMID: 27545679 Phenotypes for gene: SQSTM1 were set to Myopathy, distal, with rimmed vacuoles 617158 Review for gene: SQSTM1 was set to GREEN Added comment: PMID: 27545679 - 9 patients (4 families) with childhood/adolescent onset neurodegeneration syndrome. 7/9 patients presented with dystonia. None noted to have myopathy. Sources: Literature |
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| Dystonia and Chorea v0.67 | UBTF |
Bryony Thompson gene: UBTF was added gene: UBTF was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: UBTF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: UBTF were set to 28777933; 29300972 Phenotypes for gene: UBTF were set to Neurodegeneration, childhood-onset, with brain atrophy MIM#617672 Mode of pathogenicity for gene: UBTF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: UBTF was set to GREEN Added comment: 7 out of 11 unrelated cases with a recurrent de novo gain of function missense variant (p.Glu210Lys) have dystonia as a feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.66 | FITM2 |
Bryony Thompson changed review comment from: Three unrelated cases with a dystonia-deafness syndrome and a supporting Drosophila model. Sources: Expert list; to: 7 cases from 3 unrelated families (2 consanguineous) with a dystonia-deafness syndrome and a supporting Drosophila model. Sources: Expert list |
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| Dystonia and Chorea v0.65 | FITM2 |
Bryony Thompson gene: FITM2 was added gene: FITM2 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: FITM2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FITM2 were set to 28067622; 30214770; 30288795 Phenotypes for gene: FITM2 were set to Siddiqi syndrome MIM#618635; dystonia; deafness Review for gene: FITM2 was set to GREEN Added comment: Three unrelated cases with a dystonia-deafness syndrome and a supporting Drosophila model. Sources: Expert list |
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| Dystonia and Chorea 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 and Chorea v0.60 | MECR | Zornitza Stark Phenotypes for gene: MECR were changed from Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities to Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, MIM#617282 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.58 | ACTB | Bryony Thompson reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: Other; Publications: 25255767, 31970217, 28487785, 28849312, 29788902; Phenotypes: Dystonia, juvenile-onset MIM#607371; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.58 | MECR |
Elena Savva gene: MECR was added gene: MECR was added to Dystonia - complex. Sources: Expert Review Mode of inheritance for gene: MECR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MECR were set to PMID: 27817865; 31137067 Phenotypes for gene: MECR were set to Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities Review for gene: MECR was set to GREEN Added comment: PMID: 27817865 - 4/5 families w/ bilallelic variants reported w/ dystonia with variable features PMID: 31137067 - 1 patient w/ chet missense/PTCs and dystonia with variable features Sources: Expert Review |
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| Dystonia and Chorea v0.56 | XK |
Bryony Thompson gene: XK was added gene: XK was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: XK was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: XK were set to 11761473 Phenotypes for gene: XK were set to McLeod syndrome with or without chronic granulomatous disease MIM#300842 Review for gene: XK was set to GREEN Added comment: 5 out of 13 cases had dystonia as a feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.55 | VPS37A |
Bryony Thompson gene: VPS37A was added gene: VPS37A was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: VPS37A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS37A were set to 22717650 Phenotypes for gene: VPS37A were set to Spastic paraplegia 53, autosomal recessive MIM#614898 Review for gene: VPS37A was set to RED Added comment: Single consanguineous Arab Moslem kindred with dystonia as a feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.54 | UNC80 |
Bryony Thompson gene: UNC80 was added gene: UNC80 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: UNC80 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UNC80 were set to 26545877 Phenotypes for gene: UNC80 were set to hypotonia; severe intellectual disability; dyskinesia; dysmorphism Review for gene: UNC80 was set to RED Added comment: Two consanguineous Bedouin Israeli families homozygous for the same variantc.151C>T, p.(R51*) with dystonia as a feature of the condition. No other reported evidence for dystonia in the context of this condition. Sources: Expert list |
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| Dystonia and Chorea v0.52 | TREX1 |
Bryony Thompson gene: TREX1 was added gene: TREX1 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: TREX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TREX1 were set to 20131292 Phenotypes for gene: TREX1 were set to Aicardi-Goutieres syndrome 1, dominant and recessive MIM#225750 Review for gene: TREX1 was set to GREEN Added comment: 7 unrelated cases with dystonia as a feature of the condition, 6 biallelic and 1 de novo. Sources: Expert list |
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| Dystonia and Chorea v0.51 | TOR1AIP1 | Bryony Thompson reviewed gene: TOR1AIP1: Rating: RED; Mode of pathogenicity: None; Publications: 25425325; Phenotypes: Dystonia, Cerebellar Atrophy, Cardiomyopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.50 | SYT1 |
Bryony Thompson gene: SYT1 was added gene: SYT1 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: SYT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SYT1 were set to 30107533 Phenotypes for gene: SYT1 were set to Baker-Gordon syndrome MIM#618218 Review for gene: SYT1 was set to GREEN Added comment: 4 out of 11 cases with a de novo variant had dystonia as a feature of the phenotype. Sources: Expert list |
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| Dystonia and Chorea v0.48 | SUOX |
Bryony Thompson gene: SUOX was added gene: SUOX was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: SUOX was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SUOX were set to 9600976; 28933809; 16140720 Phenotypes for gene: SUOX were set to Sulfite oxidase deficiency MIM#272300 Review for gene: SUOX was set to GREEN Added comment: Dystonia is a feature of late-onset isolated sulfite oxidase deficiency. At least 6 cases reported with dystonia as a feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.46 | SNORD118 |
Bryony Thompson gene: SNORD118 was added gene: SNORD118 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: SNORD118 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SNORD118 were set to 27571260 Phenotypes for gene: SNORD118 were set to Leukoencephalopathy, brain calcifications, and cysts MIM#614561 Review for gene: SNORD118 was set to GREEN Added comment: At least 6 cases/families reported with dystonia as a feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.44 | SAMHD1 |
Bryony Thompson gene: SAMHD1 was added gene: SAMHD1 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: SAMHD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SAMHD1 were set to 20131292 Phenotypes for gene: SAMHD1 were set to Aicardi-Goutieres syndrome 5 MIM#612952 Review for gene: SAMHD1 was set to AMBER Added comment: Two unrelated cases reported with dystonia as a feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.42 | RNASEH2C |
Bryony Thompson gene: RNASEH2C was added gene: RNASEH2C was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: RNASEH2C was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNASEH2C were set to 20131292; 23322642 Phenotypes for gene: RNASEH2C were set to Aicardi-Goutieres syndrome 3 MIM#610329 Review for gene: RNASEH2C was set to GREEN Added comment: Three unrelated cases with dystonia as a feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.40 | RNASEH2B |
Bryony Thompson gene: RNASEH2B was added gene: RNASEH2B was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: RNASEH2B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNASEH2B were set to 20131292; 26860721 Phenotypes for gene: RNASEH2B were set to Aicardi-Goutieres syndrome 2 MIM#610181 Review for gene: RNASEH2B was set to GREEN Added comment: 3 or 4 cases with biallelic variants (one of the publications in Spanish and unsure if both cases have dystonia) with dystonia as a feature of the condition. Two other cases with dystonia as a feature, but only a single heterozygous variant was identified. Sources: Expert list |
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| Dystonia and Chorea v0.39 | RNASEH2A |
Bryony Thompson gene: RNASEH2A was added gene: RNASEH2A was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: RNASEH2A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNASEH2A were set to 20131292 Phenotypes for gene: RNASEH2A were set to Aicardi-Goutieres syndrome 4 MIM#610333 Review for gene: RNASEH2A was set to RED Added comment: Single case reported with dystonia as a feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.38 | PLP1 |
Bryony Thompson gene: PLP1 was added gene: PLP1 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: PLP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: PLP1 were set to 30046645; 19396823 Phenotypes for gene: PLP1 were set to Pelizaeus-Merzbacher disease MIM#312080 Review for gene: PLP1 was set to RED Added comment: Dystonia has been reported as a feature of PMD in two cases/families. It does not appear to be a prominent feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.36 | PDHA1 |
Bryony Thompson gene: PDHA1 was added gene: PDHA1 was added to Dystonia - complex. Sources: Literature Mode of inheritance for gene: PDHA1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: PDHA1 were set to 20002125 Phenotypes for gene: PDHA1 were set to Pyruvate dehydrogenase E1-alpha deficiency MIM#312170 Review for gene: PDHA1 was set to GREEN Added comment: At least four cases reported with dystonia as a feature of the condition. Sources: Literature |
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| Dystonia and Chorea v0.34 | PDHX |
Bryony Thompson gene: PDHX was added gene: PDHX was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: PDHX was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDHX were set to 20002125; 16566017; 17152059 Phenotypes for gene: PDHX were set to Lacticacidemia due to PDX1 deficiency MIM#245349 Review for gene: PDHX was set to GREEN Added comment: At least four cases reported with dystonia as a feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.32 | NKX2-1 |
Bryony Thompson gene: NKX2-1 was added gene: NKX2-1 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: NKX2-1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NKX2-1 were set to 24714694; 30186310 Phenotypes for gene: NKX2-1 were set to Chorea, hereditary benign MIM#118700; Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978 Review for gene: NKX2-1 was set to GREEN Added comment: At least 7 cases with dystonia as a feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.31 | MPV17 |
Bryony Thompson gene: MPV17 was added gene: MPV17 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: MPV17 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MPV17 were set to 29282788 Phenotypes for gene: MPV17 were set to Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) MIM#256810 Review for gene: MPV17 was set to RED Added comment: Dystonia is not a prominent feature of the condition. It has been reported in 4/91 (4%) of cases. There are other features that are more prominent. Sources: Expert list |
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| Dystonia and Chorea v0.30 | MMADHC |
Bryony Thompson gene: MMADHC was added gene: MMADHC was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: MMADHC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MMADHC were set to 15292234; 18385497 Phenotypes for gene: MMADHC were set to Homocystinuria, cblD type, variant 1 MIM#277410 Review for gene: MMADHC was set to RED Added comment: Single case reported with dystonia as a feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.29 | MAT1A |
Bryony Thompson gene: MAT1A was added gene: MAT1A was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: MAT1A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAT1A were set to 8770875 Phenotypes for gene: MAT1A were set to Methionine adenosyltransferase deficiency, autosomal recessive MIM#250850 Review for gene: MAT1A was set to RED Added comment: Single case reported with dystonia a feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.28 | MARS2 | Bryony Thompson Added comment: Comment on list classification: Large duplications that are not detected by WES are the only reported cause of the form of spastic ataxia caused by this gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.27 | MARS2 |
Bryony Thompson gene: MARS2 was added gene: MARS2 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: MARS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MARS2 were set to 16672289; 22448145 Phenotypes for gene: MARS2 were set to Spastic ataxia 3, autosomal recessive MIM#611390 Review for gene: MARS2 was set to GREEN Added comment: 57% of 23 cases from 17 French-Canadian spastic ataxia families had dystonia as a feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.26 | MAPT |
Bryony Thompson gene: MAPT was added gene: MAPT was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: MAPT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAPT were set to 17319286; 15883319 Phenotypes for gene: MAPT were set to Dementia, frontotemporal, with or without parkinsonism MIM#600274 Review for gene: MAPT was set to AMBER Added comment: Dystonia has been reported in two cases. Cannot find evidence that dystonia is a prominent feature associated with MAPT variants. Sources: Expert list |
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| Dystonia and Chorea v0.24 | L2HGDH |
Bryony Thompson gene: L2HGDH was added gene: L2HGDH was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: L2HGDH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: L2HGDH were set to 24753671; 18780161; 15824270; 10399870 Phenotypes for gene: L2HGDH were set to L-2-hydroxyglutaric aciduria MIM#236792 Review for gene: L2HGDH was set to GREEN Added comment: Four families with dystonia as a feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.23 | KCNQ2 |
Bryony Thompson gene: KCNQ2 was added gene: KCNQ2 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: KCNQ2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNQ2 were set to 12742592 Phenotypes for gene: KCNQ2 were set to Epileptic encephalopathy, early infantile, 7 MIM#613720 Review for gene: KCNQ2 was set to RED Added comment: Cannot find evidence that dystonia is a prominent feature of the condition. Single case reported with dystonic features from 2003 Sources: Expert list |
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| Dystonia and Chorea v0.21 | HACE1 |
Bryony Thompson gene: HACE1 was added gene: HACE1 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: HACE1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HACE1 were set to 26424145; 26437029 Phenotypes for gene: HACE1 were set to Spastic paraplegia and psychomotor retardation with or without seizures MIM#616756 Review for gene: HACE1 was set to AMBER Added comment: Two families where 1/5 and 1/3 affected cases has dystonic movements as part of their phenotype, respectively (PMID: 26424145). Members of two out of four families have spasticity/dystonia features, with no further differentiation supplied (PMID: 26437029). Sources: Expert list |
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| Dystonia and Chorea v0.20 | GAMT |
Bryony Thompson gene: GAMT was added gene: GAMT was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: GAMT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GAMT were set to 19027335 Phenotypes for gene: GAMT were set to Cerebral creatine deficiency syndrome 2 MIM#612736 Review for gene: GAMT was set to RED Added comment: Dystonia is not a prominent feature of the condition. A single case has been reported with dystonia as part of the phenotype. Sources: Expert list |
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| Dystonia and Chorea v0.18 | FBXL4 |
Bryony Thompson changed review comment from: Cannot find evidence that dystonia is a prominent feature of the condition. Sources: Expert list; to: Dystonia is a feature of the phenotype in three out of nine cases with biallelic variants. Sources: Expert list |
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| Dystonia and Chorea v0.18 | FBXL4 | Bryony Thompson edited their review of gene: FBXL4: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.18 | FBXL4 |
Bryony Thompson gene: FBXL4 was added gene: FBXL4 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: FBXL4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FBXL4 were set to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) MIM#615471 Review for gene: FBXL4 was set to RED Added comment: Cannot find evidence that dystonia is a prominent feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.17 | EARS2 |
Bryony Thompson gene: EARS2 was added gene: EARS2 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: EARS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EARS2 were set to 22492562 Phenotypes for gene: EARS2 were set to Combined oxidative phosphorylation deficiency 12 MIM#614924 Review for gene: EARS2 was set to RED Added comment: Dystonia does not appear to be a prominent feature of the condition. Sources: Expert list |
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| Dystonia and Chorea v0.15 | CHMP2B | Bryony Thompson reviewed gene: CHMP2B: Rating: RED; Mode of pathogenicity: None; Publications: 12451202; Phenotypes: Dementia, familial, nonspecific MIM#600795; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dystonia and Chorea v0.14 | CACNA1A |
Bryony Thompson gene: CACNA1A was added gene: CACNA1A was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: CACNA1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CACNA1A were set to 25468264; 23441182; 19232643; 18758887; 11344116 Phenotypes for gene: CACNA1A were set to Episodic ataxia, type 2 MIM#108500; Spinocerebellar ataxia 6 MIM#183086 Review for gene: CACNA1A was set to GREEN Added comment: At least four families where dystonia is a feature of the condition (complex dystonia phenotype), and knockout mouse model also has dystonia as a feature of the phenotype. Sources: Expert list |
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| Dystonia and Chorea v0.13 | AFG3L2 |
Bryony Thompson gene: AFG3L2 was added gene: AFG3L2 was added to Dystonia - complex. Sources: Expert list Mode of inheritance for gene: AFG3L2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AFG3L2 were set to 22964162; 16541453 Phenotypes for gene: AFG3L2 were set to Spastic ataxia 5, autosomal recessive MIM#614487 Review for gene: AFG3L2 was set to RED Added comment: Dystonia is not a prominent feature of this condition. There is a single family reported with complex dystonia. Dystonia was previously observed in a family whose affected members carried an 18p chromosomal deletion that included AFG3L2. Sources: Expert list |
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| Dystonia and Chorea v0.9 | GRN |
Bryony Thompson gene: GRN was added gene: GRN was added to Dystonia - complex_RMH. Sources: Expert list Mode of inheritance for gene: GRN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: GRN were set to Frontotemporal lobar degeneration with ubiquitin-positive inclusions, MIM#607485 Review for gene: GRN was set to GREEN Added comment: Dystonia is a reported feature of the phenotype Sources: Expert list |
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| Dystonia and Chorea v0.7 | GM2A |
Bryony Thompson gene: GM2A was added gene: GM2A was added to Dystonia - complex_RMH. Sources: Expert list Mode of inheritance for gene: GM2A was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GM2A were set to GM2-gangliosidosis, AB variant, MIM#272750 Review for gene: GM2A was set to GREEN Added comment: Dystonia is a feature of the phenotype Sources: Expert list |
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| Dystonia and Chorea v0.5 | GALT |
Bryony Thompson gene: GALT was added gene: GALT was added to Dystonia - complex_RMH. Sources: Expert list Mode of inheritance for gene: GALT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GALT were set to 30718057 Phenotypes for gene: GALT were set to Galactosemia, MIM#230400 Review for gene: GALT was set to GREEN Added comment: Dystonia can be a feature of the phenotype (PMID: 30718057). Sources: Expert list |
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| Dystonia and Chorea v0.3 | FUCA1 |
Bryony Thompson gene: FUCA1 was added gene: FUCA1 was added to Dystonia - complex_RMH. Sources: Expert list Mode of inheritance for gene: FUCA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FUCA1 were set to 31064022 Phenotypes for gene: FUCA1 were set to Fucosidosis, MIM#230000 Review for gene: FUCA1 was set to GREEN Added comment: Dystonia can be a feature of the phenotype. Dystonia was present in 9/75 Fucosidosis cases in a literature review (PMID: 31064022). Sources: Expert list |
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| Dystonia and Chorea v0.1 | ARSA |
Bryony Thompson gene: ARSA was added gene: ARSA was added to Dystonia - complex_RMH. Sources: Expert list Mode of inheritance for gene: ARSA was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ARSA were set to Metachromatic leukodystrophy, MIM#250100 Review for gene: ARSA was set to GREEN Added comment: Dystonia is a feature of the phenotype Sources: Expert list |
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| Dystonia and Chorea v0.0 | WDR45 |
Bryony Thompson gene: WDR45 was added gene: WDR45 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: WDR45 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: WDR45 were set to Neurodegeneration with brain iron accumulation 5 300894; beta-propeller protein-associated neurodegeneration; Dystonia |
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| Dystonia and Chorea v0.0 | VPS13A |
Bryony Thompson gene: VPS13A was added gene: VPS13A was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: VPS13A was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: VPS13A were set to complex parkinsonism; Choreoacanthocytosis 200150 |
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| Dystonia and Chorea v0.0 | TPK1 |
Bryony Thompson gene: TPK1 was added gene: TPK1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: TPK1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TPK1 were set to Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type); Dystonia |
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| Dystonia and Chorea v0.0 | TOR1AIP1 |
Bryony Thompson gene: TOR1AIP1 was added gene: TOR1AIP1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Red Mode of inheritance for gene: TOR1AIP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TOR1AIP1 were set to 25425325 Phenotypes for gene: TOR1AIP1 were set to Dystonia, cerebellar atrophy, and cardiomyopathy |
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| Dystonia and Chorea v0.0 | TIMM8A |
Bryony Thompson gene: TIMM8A was added gene: TIMM8A was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: TIMM8A was set to Phenotypes for gene: TIMM8A were set to Deafness-Dystonia-Optic Neuronopathy Syndrome |
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| Dystonia and Chorea v0.0 | SUCLA2 |
Bryony Thompson gene: SUCLA2 was added gene: SUCLA2 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: SUCLA2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SUCLA2 were set to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria); Dystonia |
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| Dystonia and Chorea v0.0 | SLC39A14 |
Bryony Thompson gene: SLC39A14 was added gene: SLC39A14 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: SLC39A14 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SLC39A14 were set to Hypermanganesemia with dystonia 2 617013 |
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| Dystonia and Chorea v0.0 | SLC30A10 |
Bryony Thompson gene: SLC30A10 was added gene: SLC30A10 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: SLC30A10 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SLC30A10 were set to Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease; Hypermanganesemia with dystonia, polycythemia, and cirrhosis, 613280 |
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| Dystonia and Chorea v0.0 | SLC20A2 |
Bryony Thompson gene: SLC20A2 was added gene: SLC20A2 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: SLC20A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: SLC20A2 were set to Basal ganglia calcification, idiopathic, 1 213600; Dystonia |
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| Dystonia and Chorea v0.0 | SLC19A3 |
Bryony Thompson gene: SLC19A3 was added gene: SLC19A3 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: SLC19A3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SLC19A3 were set to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2) 607483; Dystonia |
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| Dystonia and Chorea v0.0 | SERAC1 |
Bryony Thompson gene: SERAC1 was added gene: SERAC1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: SERAC1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SERAC1 were set to 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome; 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739; Lesions in the basal ganglia |
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| Dystonia and Chorea v0.0 | PTS |
Bryony Thompson gene: PTS was added gene: PTS was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: PTS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PTS were set to Hyperphenylalaninemia, BH4-deficient, A, 261640; 6-Pyruvoyltetrahydropterin Synthase Deficiency; Dystonia |
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| Dystonia and Chorea v0.0 | PLA2G6 |
Bryony Thompson gene: PLA2G6 was added gene: PLA2G6 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: PLA2G6 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PLA2G6 were set to Parkinson disease 14, autosomal recessive 612953; PLA2G6-associated neurodegeneration; Neurodegeneration with brain iron accumulation 2B 610217; Infantile neuroaxonal dystrophy 1 256600 |
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| Dystonia and Chorea v0.0 | PDGFRB |
Bryony Thompson gene: PDGFRB was added gene: PDGFRB was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: PDGFRB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: PDGFRB were set to Dystonia; Basal ganglia calcification, idiopathic, 4 615007 |
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| Dystonia and Chorea v0.0 | PDGFB |
Bryony Thompson gene: PDGFB was added gene: PDGFB was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: PDGFB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: PDGFB were set to Basal ganglia calcification, idiopathic, 5 615483 |
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| Dystonia and Chorea v0.0 | PANK2 |
Bryony Thompson gene: PANK2 was added gene: PANK2 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: PANK2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PANK2 were set to pantothenate kinase-associated neurodegeneration; Dystonia |
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| Dystonia and Chorea v0.0 | NKX6-2 |
Bryony Thompson gene: NKX6-2 was added gene: NKX6-2 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: NKX6-2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NKX6-2 were set to Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy 617560 |
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| Dystonia and Chorea v0.0 | HTRA2 |
Bryony Thompson gene: HTRA2 was added gene: HTRA2 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: HTRA2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: HTRA2 were set to 3-methylglutaconic aciduria, type VIII 617248 |
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| Dystonia and Chorea v0.0 | GNAO1 |
Bryony Thompson gene: GNAO1 was added gene: GNAO1 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: GNAO1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: GNAO1 were set to Neurodevelopmental disorder with involuntary movements, 617493 |
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| Dystonia and Chorea v0.0 | FTL |
Bryony Thompson gene: FTL was added gene: FTL was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: FTL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: FTL were set to Neurodegeneration with brain iron accumulation 3 606159 |
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| Dystonia and Chorea v0.0 | COASY |
Bryony Thompson gene: COASY was added gene: COASY was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: COASY were set to COASY protein-associated neurodegeneration; Neurodegeneration with brain iron accumulation 6 615643 |
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| Dystonia and Chorea v0.0 | C19orf12 |
Bryony Thompson gene: C19orf12 was added gene: C19orf12 was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: C19orf12 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: C19orf12 were set to mitochondrial membrane protein-associated neurodegeneration; neurodegeneration with brain iron accumulation-4; Dystonia |
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| Dystonia and Chorea v0.0 | AUH |
Bryony Thompson gene: AUH was added gene: AUH was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: AUH was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: AUH were set to 3-Methylglutaconic aciduria type 1; Dystonia |
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| Dystonia and Chorea v0.0 | ARX |
Bryony Thompson gene: ARX was added gene: ARX was added to Dystonia - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: ARX was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: ARX were set to Early infantile epileptic encephalopathy; Dystonia |
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