Undiagnosed metabolic disorders
Gene: WFS1EnsemblGeneIds (GRCh38): ENSG00000109501
EnsemblGeneIds (GRCh37): ENSG00000109501
OMIM: 606201, Gene2Phenotype
WFS1 is in 24 panels
3 reviews
Eleanor Williams (Genomics England Curator)
Comment on phenotypes: Original phenotypes were: Wolfram syndrome 1 (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Congenital hearing impairment (profound/severe); Diabetes with additional phenotypes suggestive of a monogenic aetiology; Familial diabetes; Hereditary ataxia; Inherited optic neuropathies.Created: 6 May 2021, 9:36 a.m. | Last Modified: 6 May 2021, 9:36 a.m.
Panel Version: 1.457
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, 9:35 a.m. | Last Modified: 6 May 2021, 9:35 a.m.
Panel Version: 1.456
Publications
Catherine Snow (Genomics England)
Comment on list classification: 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, 2:57 p.m. | Last Modified: 16 Oct 2019, 2:57 p.m.
Panel Version: 1.386
Sarah Leigh (Genomics England Curator)
Amber review assigned as this gene is Green on the V1 panel(s) named as a phenotype(s)Created: 6 Jan 2017, 2:05 p.m.
Amber review assigned as this gene is Green on the V1 panel(s) named as a phenotype(s)Created: 6 Jan 2017, 2:05 p.m.
Amber review assigned as this gene is Green on the V1 panel(s) named as a phenotype(s)Created: 6 Jan 2017, 2:04 p.m.
Amber review assigned as this gene is Green on the V1 panel(s) named as a phenotype(s)Created: 6 Jan 2017, 2:04 p.m.
Amber review assigned as this gene is Green on the V1 panel(s) named as a phenotype(s)Created: 6 Jan 2017, 2:04 p.m.
Amber review assigned as this gene is Green on the V1 panel(s) named as a phenotype(s)Created: 6 Jan 2017, 2:03 p.m.
Amber review assigned as this gene is Green on the V1 panel(s) named as a phenotype(s)Created: 6 Jan 2017, 2:03 p.m.
Amber review assigned as this gene is Green on the V1 panel(s) named as a phenotype(s)Created: 6 Jan 2017, 2:03 p.m.
Amber review assigned as this gene is Green on the V1 panel(s) named as a phenotype(s)Created: 6 Jan 2017, 2:03 p.m.
Amber review assigned as this gene is Green on the V1 panel(s) named as a phenotype(s)Created: 6 Jan 2017, 2:03 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Inherited optic neuropathies
Details
- Mode of Inheritance
- BOTH monoallelic and biallelic, autosomal or pseudoautosomal
- Sources
-
- Expert Review Green
- Literature
- Phenotypes
-
- Wolfram syndrome 1, OMIM:222300
- OMIM
- 606201
- Clinvar variants
- Variants in WFS1
- Penetrance
- Complete
- Publications
- Panels with this gene
-
- Mitochondrial disorders
- Retinal disorders
- DDG2P
- Monogenic nephrogenic diabetes insipidus
- Optic neuropathy
- Familial diabetes
- Adult onset neurodegenerative disorder
- Neonatal diabetes
- Bilateral congenital or childhood onset cataracts
- Likely inborn error of metabolism
- Hereditary ataxia with onset in adulthood
- Ataxia and cerebellar anomalies - narrow panel
- Possible mitochondrial disorder - nuclear genes
- Multi-organ autoimmune diabetes
- Structural eye disease
- Monogenic hearing loss
- Hereditary ataxia
- Glaucoma (developmental)
- Undiagnosed metabolic disorders
- Diabetes with additional phenotypes suggestive of a monogenic aetiology
- Monogenic diabetes
- Intellectual disability
- Familial Meniere Disease
- Childhood onset dystonia, chorea or related movement disorder
History Filter Activity
Set Phenotypes
Eleanor Williams (Genomics England Curator)Phenotypes for gene: WFS1 were changed from Wolfram syndrome 1 (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Congenital hearing impairment (profound/severe); Diabetes with additional phenotypes suggestive of a monogenic aetiology; Familial diabetes; Hereditary ataxia; Inherited optic neuropathies to Wolfram syndrome 1, OMIM:222300
Set publications
Catherine Snow (Genomics England)Publications for gene: WFS1 were set to 27604308
Entity classified by Genomics England curator
Catherine Snow (Genomics England)Gene: wfs1 has been classified as Green List (High Evidence).
panel promoted to version 1
Sarah Leigh (Genomics England Curator)Construction of “Undiagnosed Metabolic Disorders” (UDM) panel • The 614 genes from the neurometabolic gene panel (PMID: 27604308) added • Green genes downloaded from V1 metabolic panels (Cerebral folate deficiency, Congenital disorders of glycosylation, Hyperammonaemia, Ketotic hypoglycaemia, Mitochondrial disorders, Mucopolysaccharideosis, Gaucher, Fabry, Peroxisomal disorders), sources replaced with "Expert review green", then loaded as a review onto UDM panel, resulting in 367 green genes and 333 red (therefore 86 new green genes included from the additional metabolic panels that weren't previously on the UDM panel) • Downloaded green genes from all panels. Removed genes from none V1 panels. Removed genes from the metabolic panels mentioned above. Compared the remaining genes with the red genes from UDM panel. Loaded as an "Expert review Amber" review to the overlapping genes, (the panel name where the genes came from was used as the phenotype) • Used variant information from PMID 27604308 to review the genes on this panel • Reviewed genes on UDM panel with genes from Emory "Inherited Metabolic Disorders: Sequencing Panel" and UKGTN “Inborn Errors of Metabolism 226 panel”, changing status where appropriate, added 14 UKGTN genes that had not be listed before • Review 10 red genes that had not previously been reviewed, 4/10 were reclassified as green • Review the remaining 145 red genes that had not previously been reviewed (shared between reviewers EM, RF, LD, AT, HB, ON & SL), resulting in 60 green, 11 amber, 70 red, 4 I don’t know reviews) • Reviewed genes from PMID: 24816252 as a publication to genes found in the Inborn error or metabolism Genes metabolomics GWAS paper (figure 5). 2 new genes added
Set Mode of Inheritance
Sarah Leigh (Genomics England Curator)Model of inheritance for gene WFS1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Set Mode of Inheritance
Sarah Leigh (Genomics England Curator)Model of inheritance for gene WFS1 was set to BIALLELIC, autosomal or pseudoautosomal
Set Mode of Inheritance
Sarah Leigh (Genomics England Curator)Model of inheritance for gene WFS1 was set to Other - please specifiy in evaluation comments
Set Mode of Inheritance, Added New Source
Sarah Leigh (Genomics England Curator)WFS1 was added to Undiagnosed metabolic disorderspanel. Source: Expert Review Amber Model of inheritance for gene WFS1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Added New Source
Sarah Leigh (Genomics England Curator)WFS1 was added to Undiagnosed metabolic disorderspanel. Sources: Literature
Created
Sarah Leigh (Genomics England Curator)WFS1 was created by sleigh