DEMO Diabetes neonatal onset

Gene: WFS1

Green List (high evidence)

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.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Publications

• 28468959

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

• 28468959

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.