Genes in panel

Inborn errors of metabolism

Gene: WFS1

Green List (high evidence)

WFS1 (wolframin ER transmembrane glycoprotein)
EnsemblGeneIds (GRCh38): ENSG00000109501
EnsemblGeneIds (GRCh37): ENSG00000109501
OMIM: 606201, Gene2Phenotype
WFS1 is in 24 panels

3 reviews

Eleanor Williams (Genomics England Curator)

Comment 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

Catherine Snow (Genomics England)

Green List (high evidence)

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

Sarah Leigh (Genomics England Curator)

Red List (low evidence)

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

History Filter Activity

6 May 2021, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

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

6 May 2021, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: WFS1 were set to 27604308; 30171196

16 Oct 2019, Gel status: 3

Set publications

Catherine Snow (Genomics England)

Publications for gene: WFS1 were set to 27604308

16 Oct 2019, Gel status: 3

Entity classified by Genomics England curator

Catherine Snow (Genomics England)

Gene: wfs1 has been classified as Green List (High Evidence).

13 Feb 2019, Gel status: 2

Added New Source, Added New Source

Ivone Leong (Genomics England Curator)

Source NHS GMS was added to WFS1. Source London North GLH was added to WFS1.

9 Jan 2019, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

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)

8 Jan 2019, Gel status: 2

Panel promoted to version 1.0

Ellen McDonagh (Genomics England Curator)

Sarah Leigh: Associated with phenotype in O

16 Dec 2018, Gel status: 2

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Ellen McDonagh (Genomics England Curator)

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)