Objective: Wolfram syndrome is an autosomal recessive disorder characterized by early-onset diabetes mellitus, diabetes insipidus, optic atrophy and deafness. The aim of this study was to scan the WFS1 gene mutations in a Chinese Wolfram syndrome pedigree.
Methods: Eight exons and flanking introns of WFS1 gene were screened using PCR-DNA direct sequencing. Effects of the mutation on the structure and function of the WFS1 gene product, Wolframin, were evaluated by bioinformatics.
Results: A novel mutation, F417del, in the WFS1 gene was identified. The patient was homozygous of this mutation and the consanguineous parents were heterozygous. The mutation causes the lose of a non-polar amino acid, which was located in the transmembrane domain of the protein product. Bioinformatics predicted that the mutation altered the secondary structure of the transmembrane domain and decreased the hydrophobicity of F417del protein.
Conclusions: This study identified a novel mutation of WFS1 gene and represented the first cause of molecular characterization of Chinese Wolfram syndrome patients.