Optic neuropathy
Gene: WFS1PMID: 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 stressCreated: 5 May 2021, 5:54 p.m. | Last Modified: 5 May 2021, 5:54 p.m.
Panel Version: 2.38
Publications
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Wolfram syndrome
Variants in this GENE are reported as part of current diagnostic practice
Comment on mode of inheritance: Evidence that monoallelic mutations can cause a Wolfram-like phenotype in some families.Created: 11 Sep 2016, 9:24 a.m.
Comment on list classification: OA is a key element of Wolfram syndrome and this diagnosis should not be missed.Created: 11 Sep 2016, 9:22 a.m.
Comment on list classification: Optic atrophy is a feature of Wolfram syndrome, and is a green gene on multiple version 1 panels (for diabetes).Created: 7 Sep 2016, 10:16 a.m.
Phenotypes for gene: WFS1 were changed from Wolfram syndrome to Wolfram syndrome 1, OMIM:222300
Publications for gene: WFS1 were set to
Source London North GLH was added to WFS1. Rating Changed from Green List (high evidence) to Green List (high evidence)
Phenotypes for gene: WFS1 were changed from Wolfram syndrome; Wolfram syndrome to Wolfram syndrome
13.09.2016: 'Inherited optic neuropathies' was removed as a relevant disorder from the Posterior segment abnormalities gene panel (version 1.9) and this panel was approved to live. It has been internally reviewed and revised based on evidence available for each gene, and was promoted to version 1 to be used for analysis.
This gene has been classified as Green List (High Evidence).
Mode of inheritance for WFS1 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
This gene has been classified as Green List (High Evidence).
Mode of inheritance for WFS1 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for WFS1 were set to Wolfram syndrome;Wolfram syndrome
This gene has been classified as Amber List (Moderate Evidence).
WFS1 was added to Inherited optic neuropathiespanel. Sources: Expert