Ataxia and cerebellar anomalies - narrow panel
Gene: VPS41The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 11 Mar 2022, 1:56 p.m. | Last Modified: 11 Mar 2022, 1:56 p.m.
Panel Version: 2.288
Comment on list classification: New gene added by James Polke (North Thames GLH). There is sufficient evidence to promote this gene to Green at the next GSM panel update - cerebellar ataxia was evident in 9/11 patients reported to date.Created: 14 Jun 2021, 3:07 p.m. | Last Modified: 14 Jun 2021, 3:07 p.m.
Panel Version: 2.191
At least 13 individuals from 8 unrelated families (PMIDs: 32808683; 33764426; 33851776) with biallelic variants in VPS41 (7 different variants reported). All affected individuals developed cognitive impairment (GDD/ID) and dystonia, and most also had hypotonia, ataxia, and cerebellar atrophy/hypoplasia. Supported by functional data showing that variants lead to lysosomal dysfunction.Created: 14 Jun 2021, 2:55 p.m. | Last Modified: 14 Jun 2021, 2:55 p.m.
Panel Version: 2.190
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
32808683: 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.
PMID 33764426: Additional 9 individuals from 5 unrelated families reported.
Sources: NHS GMSCreated: 28 May 2021, 2:25 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Generalised Neurodevelopmental disorder; Ataxia; Dystonia
Publications
Tag Q2_21_rating was removed from gene: VPS41. Tag Q2_21_NHS_review was removed from gene: VPS41.
Source Expert Review Green was added to VPS41. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q2_21_NHS_review tag was added to gene: VPS41.
Publications for gene: VPS41 were set to 32808683; 33764426
Gene: vps41 has been classified as Amber List (Moderate Evidence).
Tag Q2_21_rating tag was added to gene: VPS41.
gene: VPS41 was added gene: VPS41 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: NHS GMS Mode of inheritance for gene: VPS41 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS41 were set to 32808683; 33764426 Phenotypes for gene: VPS41 were set to Generalised Neurodevelopmental disorder; Ataxia; Dystonia Review for gene: VPS41 was set to GREEN