DEMO Diabetes neonatal onset
Gene: WFS1
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 syndrome.Created: 11 Jan 2019, 4:27 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Variants in this GENE are reported as part of current diagnostic practice
Comment when marking as ready: Marked as Ready: 25th May 2017.Created: 25 May 2017, 10:05 a.m.
Comment on list classification: Updated rating from Red to Green: Included on the 28-gene Exeter neonatal diabetes screen. Plus personal correspondance from Elisa De-Franco (University of Exeter Medical School) who agrees that WFS1 should be included on this panel (see PMID:28468959 reporting 5 patients (2 with diabetes diagnosed under 6 months).Created: 25 May 2017, 10:04 a.m.
Some specific dominant WFS1 mutations have been shown to cause a syndromic form of neonatal diabetes in 5 unrelated patients (PMID:28468959, De Franco et al., 2017). They had diabetes diagnosed before 12 months (in 2 patients, diabetes was diagnosed before 6 months). This syndrome has a discrete pathophysiology and differs genetically and clinically from recessive Wolfram syndrome (MIM:222300).Created: 25 May 2017, 10:01 a.m.
Comment on mode of inheritance: Monoallelic mode of inheritance supported by PMID:28468959 (De Franco et al., 2017).Created: 25 May 2017, 10 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
syndromic neonatal diabetes
Publications
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.
gene: WFS1 was added gene: WFS1 was added to DEMO Diabetes - neonatal onset. Sources: Expert Review Green,NHS GMS,Other Mode of inheritance for gene: WFS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: WFS1 were set to 28468959 Phenotypes for gene: WFS1 were set to Wolfram syndrome, 222300; Syndromic neonatal diabetes