Diabetes in Wolfram syndrome: update of clinical and genetic aspects.

Mutations of the WFS1 (Wolfram syndrome 1) gene cause Wolfram syndrome, which is a rare autosomal recessive disorder characterized by juvenile diabetes mellitus, optic atrophy, deafness, and diabetes insipidus. These clinical characteristics are associated with other variable manifestations. The product encoded by the WFS1 gene, wolframin, could be involved in the endoplasmic reticulum stress response causing β-cell loss through impaired cell cycle progression and increased apoptosis. Recently, another causative gene, CISD2, has been identified from patients with a type of WS (WFS2) resulting in early optic atrophy, diabetes mellitus, deafness, decreased lifespan, and gastrointestinal ulceration, but not diabetes insipidus. The aim of this chapter is to review the current knowledge on these conditions.