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| Childhood onset dystonia, chorea or related movement disorder v1.261 | AP1S2 |
Arina Puzriakova changed review comment from: Comment on mode of inheritance: Review of literature did not reveal any confirmed affected females. Female carriers of AP1S2 variants are phenotypically normal and have mostly shown random X-inactivation. Huo et al., 2019 (PMID: 30714330) state that they identified a female patient (I-1) but this individual was not available for genetic testing and so it is unclear whether they harboured a variant on a one or both alleles. As no confirmed female cases have been reported and the allelic requirement remains elusive, the MOI should be set to the default XL (i.e. monoallelic in females may cause disease) as this will ensure that both mono and biallelic variants are picked up in females by the pipeline.; to: Comment on mode of inheritance: Review of literature did not reveal any confirmed affected females. Female carriers of AP1S2 variants are phenotypically normal and have mostly shown random X-inactivation. Huo et al., 2019 (PMID: 30714330) state that they identified a female patient (I-1) but this individual was not available for genetic testing and so it is unclear whether they harboured a variant on a one or both alleles. As it is not known definitively whether females require a variant on each allele of this gene in order to be affected, the MOI should be set to the default XL (i.e. monoallelic in females may cause disease). |
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| Childhood onset dystonia, chorea or related movement disorder v1.237 | VPS4A | Arina Puzriakova changed review comment from: Comment on mode of inheritance: Setting MOI to 'Monoallelic' as only one biallelic case reported to date, and patients with biallelic variants would still be picked up by the Genomics England pipeline.; to: Comment on mode of inheritance: Setting MOI to 'Monoallelic' as only one biallelic case reported to date. Added 'watchlist_moi tag to allow monitoring for additional cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset dystonia, chorea or related movement disorder v1.159 | AP1S2 |
Arina Puzriakova Added comment: Comment on mode of inheritance: Review of literature did not reveal any confirmed affected females. Female carriers of AP1S2 variants are phenotypically normal and have mostly shown random X-inactivation. Huo et al., 2019 (PMID: 30714330) state that they identified a female patient (I-1) but this individual was not available for genetic testing and so it is unclear whether they harboured a variant on a one or both alleles. As no confirmed female cases have been reported and the allelic requirement remains elusive, the MOI should be set to the default XL (i.e. monoallelic in females may cause disease) as this will ensure that both mono and biallelic variants are picked up in females by the pipeline. |
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| Childhood onset dystonia, chorea or related movement disorder v1.125 | VPS16 |
Arina Puzriakova Added comment: Comment on mode of inheritance: While most cases of VPS16-related dystonia have been due to heterozygous variants, one Chinese consanguineous family with dystonia has been found to harbour a homozygous missense variant (PMID:27174565). In view of only one biallelic case, MOI has been set as 'Monoallelic' - patients with biallelic variants would still be picked up by the Genomics England pipeline. Furthermore, biallelic VPS16 variants have been linked to a mucopolysaccharidosisâlike disease - reviewed on the 'Lysosomal storage disorder' (R276) panel. |
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| Childhood onset dystonia, chorea or related movement disorder v1.83 | VPS4A | Arina Puzriakova Added comment: Comment on mode of inheritance: Setting MOI to 'Monoallelic' as only one biallelic case reported to date, and patients with biallelic variants would still be picked up by the Genomics England pipeline. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset dystonia, chorea or related movement disorder v1.81 | VPS4A |
Arina Puzriakova gene: VPS4A was added gene: VPS4A was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Expert Review for-review tags were added to gene: VPS4A. Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: VPS4A were set to 33186545; 33186543; 33460484 Phenotypes for gene: VPS4A were set to CIMDAG syndrome Review for gene: VPS4A was set to GREEN Added comment: Gene currently not associated with any phenotype in OMIM (last edited: 20/12/2019) or Gene2Phenotype. - PMID: 33186545 (2020) - Six unrelated individuals with de novo missense variants (c.850A>T, c.850A>G, c.616G>A) affecting the ATPase domain of VPS4A. Clinical features include severe DD and profound ID (6/6), hypotonia (5/6), microcephaly (6/6), dystonia (5/6), congenital cataracts (4/5), epilepsy (3/6), anaemia (3/6 - dyserythropoietic in 2), and structural brain abnormalities including cerebellar hypoplasia (5/6) or severe cerebral atrophy (1/6). Some functional data indicating a dominant-negative effect. - PMID: 33186543 (2020) - Three unrelated individuals with congenital dyserythropoietic anaemia, severe neurodevelopmental delay, and dystonia. Two patients harboured different de novo variants (c.850A>T, c.608G>A) in the ATPase domain, while the third had a homozygous alteration (c.83C>T) occurring in the N-terminal microtubule interacting and trafficking domain of VPS4A. The first two individuals congenital microcephaly with brain MRI showing white matter and cerebral volume loss, thin corpus callosum, and ponto-cerebellar atrophy. One individual also displayed a seizure disorder and congenital cataracts. The case with the biallelic variant presented with a milder hematologic phenotype and had macrocephaly (rather than microcephaly) and delayed white matter myelination. Functional studies support pathogenicity. - PMID: 33460484 (2021) - One child with a a severe neurodevelopmental disorder and congenital haemolytic anaemia but no overt sign of dyserythropoiesis, associated with a de novo variant (c.850A>T) in VPS4A. Other features include microcephaly (-2.5 SD), choreodystonic movements, and bilateral cataract. Brain MRI showed cerebral atrophy, thin dysplastic corpus callosum, basal ganglia atrophy, brainstem hypoplasia, cerebellar hypoplasia and dysplasia Sources: Expert Review |
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| Childhood onset dystonia, chorea or related movement disorder v1.78 | ICK | Arina Puzriakova Phenotypes for gene: ICK were changed from Endocrine-cerebroosteodysplasia, 612651; ECO; short-rib thoracic dysplasia with polydactyly (SRTD) to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset dystonia, chorea or related movement disorder v1.0 | ICK | Louise Daugherty Tag new-gene-name tag was added to gene: ICK. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset dystonia, chorea or related movement disorder v1.0 | ICK | Louise Daugherty commented on gene: ICK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset dystonia, chorea or related movement disorder v0.239 | NPC1 | Louise Daugherty Phenotypes for gene: NPC1 were changed from Niemann-Pick disease, type C1; Niemann-Pick disease, type D to Niemann-Pick disease, type C1, 257220; Niemann-Pick disease, type D, 257220 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset dystonia, chorea or related movement disorder v0.85 | NPC1 | Ellen McDonagh Phenotypes for gene: NPC1 were changed from to Niemann-Pick disease, type C1; Niemann-Pick disease, type D | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset dystonia, chorea or related movement disorder v0.7 | ICK |
Ellen McDonagh Source PanelApp was added to ICK. Mode of inheritance for gene ICK was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Endocrine-cerebroosteodysplasia, 612651; ECO; short-rib thoracic dysplasia with polydactyly (SRTD) for gene: ICK Publications for gene ICK were changed from to 27466187; 19185282; 27069622 |
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| Childhood onset dystonia, chorea or related movement disorder v0.1 | PSEN1 |
Ellen McDonagh gene: PSEN1 was added gene: PSEN1 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: South West GLH Mode of inheritance for gene: PSEN1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PSEN1 were set to Alzheimer disease, type 3, 607822; Pick disease, 172700; Dementia, frontotemporal 600274; Cardiomyopathy, dilated, 1U, 613694 |
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| Childhood onset dystonia, chorea or related movement disorder v0.1 | NPC2 |
Ellen McDonagh Source South West GLH was added to NPC2. Mode of inheritance for gene NPC2 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Niemann-pick disease, type C2, 607625 for gene: NPC2 |
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| Childhood onset dystonia, chorea or related movement disorder v0.0 | ICK |
Ellen McDonagh gene: ICK was added gene: ICK was added to Childhood onset dystonia or chorea or related movement disorder. Sources: London North GLH,Expert Review Red Mode of inheritance for gene: ICK was set to |
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