Novel missense WFS1 variant causing autosomal dominant atypical Wolfram syndrome

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.

Automated summary

This study presents the deep phenotyping analysis of a mother and son carrying a novel WFS1 gene variant. Both the patient and the mother showed sensorineural hearing loss and mild non-progressive vision loss with optic nerve atrophy. The WFS1 variant was identified through a broader inherited retinal dystrophy panel.