Likely inborn error of metabolism - targeted testing not possible
Gene: WFS1Comment on phenotypes: Previous phenotypes were: Diabetes with additional phenotypes suggestive of a monogenic aetiology;Inherited optic neuropathies;Wolfram syndrome 1, 222300;Mitochondrial respiratory chain disorders caused by nuclear variants only;Hereditary ataxia;Familial diabetes;Congenital hearing impairment (profound/severe)Created: 6 May 2021, 9:40 a.m. | Last Modified: 6 May 2021, 9:40 a.m.
Panel Version: 2.131
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: 6 May 2021, 9:37 a.m. | Last Modified: 6 May 2021, 9:37 a.m.
Panel Version: 2.129
Publications
This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Promoted from Amber to Green. WFS1 is associated with an appropriate phenotype on OMIM and Gene2Phenotype. There are >3 unrelated cases listed on OMIM. Therefore, enough evidence for this gene to be promoted to Green status.Created: 16 Oct 2019, 2:55 p.m. | Last Modified: 16 Oct 2019, 2:55 p.m.
Panel Version: 1.360
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Wolfram syndrome 1, 222300; Wolfram-like syndrome, autosomal dominant, 614296; Diabetes mellitus, noninsulin-dependent, association with, 125853
Publications
Initial gene list and info collated by Carl Fratter (Oxford University Hospitals NHS Trust) January 2019 on behalf of the GMS Mitochondrial specialist test group.Created: 23 Jul 2019, 10:13 a.m. | Last Modified: 23 Jul 2019, 10:13 a.m.
Panel Version: 1.412
Phenotypes for gene: WFS1 were changed from Diabetes with additional phenotypes suggestive of a monogenic aetiology; Inherited optic neuropathies; Wolfram syndrome 1, 222300; Mitochondrial respiratory chain disorders caused by nuclear variants only; Hereditary ataxia; Familial diabetes; Congenital hearing impairment (profound/severe) to Wolfram syndrome 1, OMIM:222300; Wolfram-like syndrome, autosomal dominant, OMIM:614296; Diabetes mellitus, noninsulin-dependent, association with, OMIM:125853
Publications for gene: WFS1 were set to 27604308; 30171196
Publications for gene: WFS1 were set to 27604308
Gene: wfs1 has been classified as Green List (High Evidence).
Source NHS GMS was added to WFS1. Source London North GLH was added to WFS1.
Phenotypes for gene: WFS1 were changed from Diabetes with additional phenotypes suggestive of a monogenic aetiology; Inherited optic neuropathies; Wolfram syndrome 1 (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Hereditary ataxia; Familial diabetes; Congenital hearing impairment (profound/severe) to Diabetes with additional phenotypes suggestive of a monogenic aetiology; Inherited optic neuropathies; Wolfram syndrome 1, 222300; Mitochondrial respiratory chain disorders caused by nuclear variants only; Hereditary ataxia; Familial diabetes; Congenital hearing impairment (profound/severe)
Sarah Leigh: Associated with phenotype in O
gene: WFS1 was added gene: WFS1 was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: WFS1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: WFS1 were set to 27604308 Phenotypes for gene: WFS1 were set to Diabetes with additional phenotypes suggestive of a monogenic aetiology; Inherited optic neuropathies; Wolfram syndrome 1 (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Hereditary ataxia; Familial diabetes; Congenital hearing impairment (profound/severe)