C2orf37 Mutational Spectrum in Woodhouse-Sakati Syndrome Patients

The study investigated the mutational spectrum of the C2orf37 gene in Woodhouse–Sakati syndrome (WSS), a rare autosomal recessive disorder characterized by hypogonadism, deafness, alopecia, mental retardation, diabetes mellitus, and progressive extrapyramidal defects. Researchers analyzed seven new cases from three ethnic backgrounds, identifying novel mutations in each of the four families studied, including three nonsense mutations and one splice site ablation. The study doubled the number of known mutations for WSS and confirmed that truncating mutations in C2orf37 are the sole cause of the syndrome. Additionally, the research suggested that mutations in C2orf37 do not significantly contribute to cases with isolated symptoms like deafness and dystonia. The findings highlighted the lack of correlation between the clinical expressivity of WSS and the mutation sites, indicating that all truncating mutations are equally null, and emphasized the role of genetic modifiers in the disease's variability.