Familial diabetes
Gene: WFS1PMID: 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
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.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Variants in this GENE are reported as part of current diagnostic practice
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.
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.
Phenotypes for gene: WFS1 were changed from Wolfram syndrome, 222300 to Wolfram syndrome, OMIM:222300
Publications for gene: WFS1 were set to 27217304; 27185633
Mode of inheritance for WFS1 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of inheritance for WFS1 was changed to Other - please specifiy in evaluation comments
Phenotypes for WFS1 were set to Wolfram syndrome, 222300
Publications for WFS1 were set to 27217304; 27185633
Mode of inheritance for WFS1 was changed to BIALLELIC, autosomal or pseudoautosomal
This gene has been classified as Green List (High Evidence).
WFS1 was added to Familial diabetespanel. Sources: Radboud University Medical Center, Nijmegen