A homozygous missense mutation of WFS1 gene causes Wolfram's syndrome without hearing loss in an Iranian family (a report of clinical heterogeneity)

摘要

Background Wolfram's syndrome (WFS) is a hereditary (autosomal recessive) neurodegenerative disorder. The clinical features are related to diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD) with other variable clinical manifestations. Pathogenic variants in the WFS1 gene, encoding wolframin, are known to be the main cause of Wolfram's syndrome. In this study, we present the clinical and genetic characteristics of two WFS patients from an Iranian family. Methods The mutation screening was performed by polymerase chain reaction (PCR) followed by direct Sanger sequencing of all exons from two affected WFS. Results The complete Sanger sequencing of the WFS1 gene detected a homozygous missense variant, c.2207GA (p.Gly736Asp), in the eighth exon of the WFS1 gene. Both cases developed all the major symptoms of the disease, interestingly, except hearing loss. Conclusions Because of the rarity and clinical heterogeneity of WFS, the molecular genetic assay is essential to confirm the diagnosis and management of the WFS patients.