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| Childhood onset dystonia, chorea or related movement disorder v8.9 | ATP2B2 | Achchuthan Shanmugasundram Classified gene: ATP2B2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset dystonia, chorea or related movement disorder v8.9 | ATP2B2 | Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated patients reported with other movement disorders including dystonia (in one patient). As this is a small subset of total patients reported with neurological/ neurodevelopmental phenotypes (14 patients from 13 unrelated families), this gene should be rated amber with current evidence. However, 'watchlist' tag has been added to review the gene in light of any new evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset dystonia, chorea or related movement disorder v8.9 | ATP2B2 | Achchuthan Shanmugasundram Gene: atp2b2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset dystonia, chorea or related movement disorder v8.8 | ATP2B2 |
Achchuthan Shanmugasundram gene: ATP2B2 was added gene: ATP2B2 was added to Childhood onset dystonia, chorea or related movement disorder. Sources: Literature watchlist tags were added to gene: ATP2B2. Mode of inheritance for gene: ATP2B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP2B2 were set to 29655659; 37675773; 39367743 Phenotypes for gene: ATP2B2 were set to neurodevelopmental disorder, MONDO:0700092; cerebellar ataxia, MONDO:0000437; epilepsy, MONDO:0005027; intellectual disability,MONDO:0001071; inherited dystonia, MONDO:0044807 Mode of pathogenicity for gene: ATP2B2 was set to Other Review for gene: ATP2B2 was set to AMBER Added comment: PMID:29655659 (2018) reported a novel missense variant (p.Val1143Phe) in PMCA2/ ATP2B2 gene in a 27-year old male patient presenting with congenital cerebellar ataxia but with no overt signs of deafness. This patient presented with delayed motor development requesting clinical attention at age 5 months, had dysmetria and intentional tremor at age 3 and showed obvious gait ataxia at age 4. The patient was also reported with impaired speech and moderate intellectual disability. Brain MRI studies revealed global cerebellar atrophy without cortical and brainstem involvement. PMID:37675773 (2023) reported seven individuals with rare, predicted deleterious heterozygous ATP2B2 variants, including 5 missense substitutions and 2 frameshift variants. De novo status was confirmed for six of these variants. All individuals displayed a spectrum of neurological abnormalities ranging from ataxia (5/7 patients) and other movement disorders including dystonic features (3 patients) to complex neurodevelopmental manifestations with intellectual disability, global developmental delay, and seizures (6 patients). Two cases with recurrent amino-acid variation showed distinctive overlap with cerebellar atrophy-associated ataxia and epilepsy. In cell-based studies, all variants caused significant alterations in cytosolic calcium handling with both loss- and gain-of-function effects. PMID:39367743 (2025) reported six previously unreported patients from five unrelated families with four different missense variants and one frameshift variant (p.Leu1089GlnfsTer60). All missense variants were confirmed de novo, while the frameshift variant is paternally inherited in one and of unknown inheritance in other. These patients shared phenotypic features with the previously described patients including developmental delay and intellectual disability (all six patients), cognitive disturbances, autistic features epilepsy (3 patients), ataxia (3 patients) and other movement disorders (one patient). Striking cerebellar atrophy was observed in one affected individual. In total, there are 13 patients (from 12 families) with (global) developmental delay/ intellectual disability, 9 patients (from eight families) with seizures, 9 patients (from nine families) with ataxia and 4 patients (from four families) reported with other movement disorders including dystonia. This gene has been associated with hearing loss in both OMIM (MIM #619804, last accessed 29 July 2026) and ClinGen ('Definitive' rating for autosomal dominant nonsyndromic hearing loss (MONDO:0019587) by Hearing Loss GCEP), but not with the neurological/ neurodevelopmental phenotypes in these resources. Sources: Literature |
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