Genes in panel

Ataxia and cerebellar anomalies - narrow panel

Gene: VPS41

Amber List (moderate evidence)

VPS41 (VPS41, HOPS complex subunit)
EnsemblGeneIds (GRCh38): ENSG00000006715
EnsemblGeneIds (GRCh37): ENSG00000006715
OMIM: 605485, Gene2Phenotype
VPS41 is in 5 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

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

James Polke (North Thames GLH)

Green List (high evidence)

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 GMS
Created: 28 May 2021, 2:25 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Generalised Neurodevelopmental disorder; Ataxia; Dystonia

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Generalised Neurodevelopmental disorder
  • Ataxia
  • Dystonia
Tags
Q2_21_rating
OMIM
605485
Clinvar variants
Variants in VPS41
Penetrance
None
Publications
Panels with this gene

History Filter Activity

14 Jun 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: VPS41 were set to 32808683; 33764426

14 Jun 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: vps41 has been classified as Amber List (Moderate Evidence).

14 Jun 2021, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: VPS41.

28 May 2021, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

James Polke (North Thames GLH)

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