Genes in panel

Hereditary ataxia - adult onset

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)

I don't know

Comment on list classification: New gene added by James Polke (North Thames GLH). There are sufficient unrelated families with ataxia (9/11 patients) and VPS41 variants to rate Green - but this appears to be a childhood-onset condition. There is one older subject (22-year-old male - PMID:33764426) for whom the age of onset is not indicated but can probably be inferred by comparison with other cases.

Inclusion may allow for identification of edge cases, but overall VPS41 will be flagged for GMS review to assess whether this is justified.
Created: 14 Jun 2021, 3:41 p.m. | Last Modified: 14 Jun 2021, 3:41 p.m.
Panel Version: 2.72
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, 3:39 p.m. | Last Modified: 14 Jun 2021, 3:39 p.m.
Panel Version: 2.71

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, 2:28 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_expert_review Q2_21_NHS_review
OMIM
605485
Clinvar variants
Variants in VPS41
Penetrance
None
Publications
Panels with this gene

History Filter Activity

13 Dec 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_NHS_review tag was added to gene: VPS41.

14 Jun 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: VPS41 were set to 32367058; 33875678

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

Removed Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_rating was removed from gene: VPS41. Tag Q2_21_expert_review tag was added to gene: VPS41.

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 Hereditary ataxia - adult onset. Sources: NHS GMS Mode of inheritance for gene: VPS41 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS41 were set to 32367058; 33875678 Phenotypes for gene: VPS41 were set to Generalised Neurodevelopmental disorder; Ataxia; Dystonia Review for gene: VPS41 was set to GREEN