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Updated: Sep 26, 2025

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Novel missense WFS1 variant causing autosomal dominant atypical Wolfram syndrome
Hailey Mair1, Nicholas Fowler1, Maria E Papatzanaki2
1Department of Ophthalmology and Visual Sciences-Ophthalmic Genetics Service, University of Kentucky, Lexington, Kentucky, USA.
Background:
In contrast to the classic autosomal recessive Wolfram syndrome, Wolfram-like syndrome (WLS) is an autosomal dominant disease caused by heterozygous variants in the WFS1 gene. Here, we present deep phenotyping of a mother and son with a WFS1 variant NM_006005.3:c.2508 G > T, p. (Lys836Asn) detected with next-generation sequencing, which is novel at the nucleotide level. In this Greek family, the proband and mother had sensorineural hearing loss and mild non-progressive vision loss with optic nerve atrophy. An initial optic atrophy panel that did not test for WFS1 was unremarkable, but a broader inherited retinal dystrophy panel found the WFS1 variant.
Conclusion:
This study highlights the importance of including WFS1 sequencing in the evaluation of optic nerve atrophy to discover syndromic conditions.
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