Cold Spring Harb Mol Case Stud. 2023 Feb 13:mcs.a006259. doi: 10.1101/mcs.a006259. Online ahead of print.
Biallelic variants in the WFS1 gene are associated with Wolfram syndrome. However, recent publications document that heterozygous variants can lead to a variety of phenotypes, such as Wolfram-like syndrome or isolated features of Wolfram syndrome. In this case report, we present a male patient with a history of congenital cataracts and subjective complaints of muscle weakness. Clinical assessment demonstrated normal muscle strength, and genomic, biochemical, electrophysiologic and muscle biopsy studies did not identify a potential cause of the proband’s perceived muscle weakness. Whole exome sequencing identified a novel de novo variant in the WFS1 gene (c.1243G>T), representing one of only several patients in the published literature with isolated congenital cataracts and a heterozygous WFS1 variant. The variety of phenotypes associated with heterozygous variants in WFS1 suggest that this gene should be considered as a cause of both dominant and biallelic/recessive forms of disease. Future research should focus on elucidating the mechanism(s) of disease and variable expressivity in WFS1 in order to improve our ability to provide patients and families with anticipatory guidance about the disease, including appropriate screening and medical interventions.