Neonatal diabetes
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.
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
Phenotypes for gene: WFS1 were changed from Syndromic neonatal diabetes; Wolfram syndrome, 222300 to Wolfram-like syndrome, autosomal dominant, OMIM:614296
Phenotypes for gene: WFS1 were changed from Syndromic neonatal diabetes to Syndromic neonatal diabetes; Wolfram syndrome, 222300
Source NHS GMS was added to WFS1. Rating Changed from Green List (high evidence) to Green List (high evidence)
Promoted panel to Version 1: 31st May 2017. This panel is largely aligned with the Exeter Molecular Genetics Laboratory neonatal diabetes screen. Note that 8 genes feature on the Exeter 8-gene panel for patients with 'neonatal diabetes and autoimmune disease' (FOXP3, IL2RA, ITCH, LRBA, SIRT1, STAT1, STAT3 and STAT5). ITCH, SIRT1, STAT1 and STAT5A/B do not feature on this panel following correspondance with Elisa De-Franco (University of Exeter Medical School) that, at the time of curation, none of the patients with mutations in ITCH, SIRT1, STAT1 and STAT5b had diabetes diagnosed in the neonatal period, and therefore there is currently insufficient evidence to include these genes in this neonatal diabetes panel.
Phenotypes for WFS1 were set to Syndromic neonatal diabetes
Mode of inheritance for WFS1 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Mode of inheritance for WFS1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
WFS1 was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: Other
WFS1 was created by rfoulger