Familial diabetes
Gene: WFS1EnsemblGeneIds (GRCh38): ENSG00000109501
EnsemblGeneIds (GRCh37): ENSG00000109501
OMIM: 606201, Gene2Phenotype
WFS1 is in 24 panels
5 reviews
Eleanor Williams (Genomics England Curator)
PMID: 33693650 - Panfili et al 2021 - report an additional case of an 11 year old patient with Wolfram syndrome (diabetes mellitus and initial signs of optic atrophy) in which 2 novel variants in WFS1, c.316-1G > A (in intron 3) and c.757A > T (in exon 7), were identified by WES. Both are predicted to produce truncated and inactive protein. One variant was inherited from each parent. Most disease associated variants to date have been found in exon 8. Wildtype WFS1 protein was absent in peripheral blood mononuclear cells of the proband and there was no evidence of ER stress activation but very high levels of proinflammatory cytokines and a high ratio of proinflammatory T helper type 17 cells to regulatory T cells was found, suggesting that WFS1 deficiency may cause effects other than alterations in unfolded protein response (UPR) signaling pathways related to ER stress.Created: 5 May 2021, 5:50 p.m. | Last Modified: 5 May 2021, 5:50 p.m.
Panel Version: 1.59
Publications
Ivone Leong (Genomics England Curator)
Initial gene list and info collated by Sian Ellard, University of Exeter Medical School, August 2018 on behalf of the GMS Endocrinology specialist test group. Gene Symbol submitted: WFS1; Suggested intial gene rating: Green; Evidence for inclusion: none given; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given; Phenotypes: Wolfram syndromeCreated: 11 Jan 2019, 10:04 a.m.
Sian Ellard (University of Exeter Medical School)
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Variants in this GENE are reported as part of current diagnostic practice
Sarah Leigh (Genomics England Curator)
Comment on mode of inheritance: Biallelic WFS1 variants are most commonly associated with Wolfram syndrome. However, heterozygous dominant negative WFS1 variants are associated with a rare form of Wolfram syndrome with subtle phenotypic differences. Comment from Sian Ellard (paper in preparation)Created: 5 Jul 2016, 7:46 a.m.
Ellen McDonagh (Genomics England Curator)
Comment on mode of inheritance: Changed from 'other' to both to capture these variants in tiering.Created: 3 Apr 2017, 5:05 p.m.
Comment on list classification: Promoted from red to green due to expert review and further supporting evidence on OMIM.Created: 28 Jun 2016, 3:11 p.m.
Details
- Mode of Inheritance
- BOTH monoallelic and biallelic, autosomal or pseudoautosomal
- Sources
-
- NHS GMS
- Expert Review Green
- Radboud University Medical Center, Nijmegen
- Phenotypes
-
- Wolfram syndrome, OMIM:222300
- OMIM
- 606201
- Clinvar variants
- Variants in WFS1
- Penetrance
- Complete
- Publications
- Panels with this gene
-
- Undiagnosed metabolic disorders
- Monogenic diabetes
- Intellectual disability
- Childhood onset dystonia, chorea or related movement disorder
- DDG2P
- Retinal disorders
- Monogenic nephrogenic diabetes insipidus
- Optic neuropathy
- Structural eye disease
- Adult onset neurodegenerative disorder
- Familial diabetes
- Ataxia and cerebellar anomalies - narrow panel
- Likely inborn error of metabolism
- Mitochondrial disorders
- Hereditary ataxia with onset in adulthood
- Multi-organ autoimmune diabetes
- Monogenic hearing loss
- Hereditary ataxia
- Possible mitochondrial disorder - nuclear genes
- Glaucoma (developmental)
- Neonatal diabetes
- Diabetes with additional phenotypes suggestive of a monogenic aetiology
- Familial Meniere Disease
- Bilateral congenital or childhood onset cataracts
History Filter Activity
Set Phenotypes
Eleanor Williams (Genomics England Curator)Phenotypes for gene: WFS1 were changed from Wolfram syndrome, 222300 to Wolfram syndrome, OMIM:222300
Set publications
Eleanor Williams (Genomics England Curator)Publications for gene: WFS1 were set to 27217304; 27185633
Set Mode of Inheritance
Ellen McDonagh (Genomics England Curator)Mode of inheritance for WFS1 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Set Mode of Inheritance
Sarah Leigh (Genomics England Curator)Mode of inheritance for WFS1 was changed to Other - please specifiy in evaluation comments
Set Phenotypes
Ellen McDonagh (Genomics England Curator)Phenotypes for WFS1 were set to Wolfram syndrome, 222300
Set publications
Ellen McDonagh (Genomics England Curator)Publications for WFS1 were set to 27217304; 27185633
Set Mode of Inheritance
Ellen McDonagh (Genomics England Curator)Mode of inheritance for WFS1 was changed to BIALLELIC, autosomal or pseudoautosomal
Gene classified by Genomics England curator
Ellen McDonagh (Genomics England Curator)This gene has been classified as Green List (High Evidence).
Added New Source
GEL ()WFS1 was added to Familial diabetespanel. Sources: Radboud University Medical Center, Nijmegen