Syndromic Retinopathy

Gene: WFS1

Green List (high evidence)

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: 5 May 2021, 12:40 p.m. | Last Modified: 5 May 2021, 12:40 p.m.

Panel Version: 0.7505

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Wolfram syndrome 1, OMIM:222300

Publications

• 33693650

Green List (high evidence)

Genotype-phenotype correlation is unclear. However, PTVs in both alleles seems to cause a more severe and with earlier onset disease. Biallelic LoF variants cause Wolfram syndrome. Two families reported with dominant inheritance (GeneReviews 2013; Matsunaga, K. et al., 2014).

Created: 3 Mar 2020, 12:31 a.m. | Last Modified: 3 Mar 2020, 12:31 a.m.

Panel Version: 0.1590

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
?Cataract 41; Deafness, autosomal dominant 6/14/38; Wolfram syndrome 1; Wolfram-like syndrome, autosomal dominant; {Diabetes mellitus, noninsulin-dependent, association with}

Publications

• PMID: 25211237