Background: Wolfram syndrome(WS) is a rare, progressive, neurodegenerative disorder with an autosomal recessive pattern of inheritance, characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness.The gene for WS, WFS1, is identified on human chromosome 4p16, encoding a transmembrane protein, if mutated, which can also cause autosomal dominant deafness 6 (DFNA6), also known as DFNA14 or DFNA38.Most WS patients carry mutations in this gene, and ~162 mutations in WFS1 have been confirmed to date, in which non-synonymous single nucleotide polymorphisms(nsSNPs) are the most common forms of genetic variations.Nonetheless, there is poor knowledge on the relationship between the geno-type and function of nsSNPs in the other single amino acid substitutions of the WFS1 gene.