Diabetes with additional phenotypes suggestive of a monogenic aetiology
Gene: WFS1EnsemblGeneIds (GRCh38): ENSG00000109501
EnsemblGeneIds (GRCh37): ENSG00000109501
OMIM: 606201, Gene2Phenotype
WFS1 is in 24 panels
4 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, 5:46 p.m. | Last Modified: 5 May 2021, 5:46 p.m.
Panel Version: 1.60
Sian Ellard (University of Exeter Medical School)
Ellen McDonagh (Genomics England Curator)
Comment on mode of inheritance: Changed from 'other' to capture these variants in tiering.Created: 3 Apr 2017, 5:06 p.m.
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: 22 Jul 2016, 12:08 p.m.
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.
Details
- Mode of Inheritance
- BOTH monoallelic and biallelic, autosomal or pseudoautosomal
- Sources
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- Expert Review Green
- Eligibility statement prior genetic testing
- Radboud University Medical Center, Nijmegen
- Phenotypes
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- Wolfram syndrome, OMIM:222300
- Deafness, autosomal dominant 6/14/38, OMIM:600965
- Wolfram-like syndrome, autosomal dominant, OMIM:614296
- {Diabetes mellitus, noninsulin-dependent, association with}, OMIM:125853
- ?Cataract 41, OMIM:116400
- diabetes insipidus or optic atrophy
- OMIM
- 606201
- Clinvar variants
- Variants in WFS1
- Penetrance
- Complete
- Publications
- Panels with this gene
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- Mitochondrial disorders
- Retinal disorders
- DDG2P
- Monogenic nephrogenic diabetes insipidus
- Optic neuropathy
- Familial diabetes
- Adult onset neurodegenerative disorder
- Neonatal diabetes
- Bilateral congenital or childhood onset cataracts
- Likely inborn error of metabolism
- Hereditary ataxia with onset in adulthood
- Ataxia and cerebellar anomalies - narrow panel
- Possible mitochondrial disorder - nuclear genes
- Multi-organ autoimmune diabetes
- Monogenic diabetes
- Structural eye disease
- Monogenic hearing loss
- Hereditary ataxia
- Glaucoma (developmental)
- Undiagnosed metabolic disorders
- Diabetes with additional phenotypes suggestive of a monogenic aetiology
- Intellectual disability
- Familial Meniere Disease
- Childhood onset dystonia, chorea or related movement disorder
History Filter Activity
Set Phenotypes
Eleanor Williams (Genomics England Curator)Phenotypes for gene: WFS1 were changed from Wolfram syndrome, 222300; Deafness, autosomal dominant 6/14/38, 600965; Wolfram-like syndrome, autosomal dominant, 614296; {Diabetes mellitus, noninsulin-dependent, association with}, 125853; ?Cataract 41,116400; Deafness,autosomal dominant 6/14/38, 600965; Wolfram syndrome, 222300; {Diabetes mellitus, noninsulin-dependent,association with}; diabetes insipidus or optic atrophy to Wolfram syndrome, OMIM:222300; Deafness, autosomal dominant 6/14/38, OMIM:600965; Wolfram-like syndrome, autosomal dominant, OMIM:614296; {Diabetes mellitus, noninsulin-dependent, association with}, OMIM:125853; ?Cataract 41, OMIM:116400; diabetes insipidus or optic atrophy
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
panel promoted to version 1
Ellen McDonagh (Genomics England Curator)25th July 2016: Panel revised acccording to expert review, further evidence sources and comparison with the Familial Diabetes version 1 panel. Promoted to version 1.
Gene classified by Genomics England curator
Ellen McDonagh (Genomics England Curator)This gene has been classified as Green List (High Evidence).
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 Other - please specifiy in evaluation comments
Gene classified by Genomics England curator
Chris Boustred (Genomics England)This gene has been classified as Green List (High Evidence).
Added New Source
Ellen McDonagh (Genomics England Curator)WFS1 was added to Diabetes with additional phenotypes suggestive of a monogenic aetiologypanel. Sources: Eligibility statement prior genetic testing
Added New Source
Ellen McDonagh (Genomics England Curator)WFS1 was added to Diabetes with additional phenotypes suggestive of a monogenic aetiologypanel. Sources: Radboud University Medical Center, Nijmegen