WFS1 gene mutation search in depressive patients: detection of five missense polymorphisms but no association with depression or bipolar affective disorder

Background: Wolfram syndrome (WFS) is an autosomal recessive neurodegenerative disorder. Recently, the WFS1 gene was isolated, and approximately 80% of the mutations responsible for WFS were found in exon 8 of WFS1. It has been noted that heterozygous carriers of the WFS gene are 26-fold more likely to be hospitalized for depression, and it has been estimated that approximately 25% of all people hospitalized for depression may carry the WFS gene(s). Methods: We searched for mutations in exon 8 of WFS1 in 30 depressive patients with a history of hospitalization and whose age at onset was under 40 years. We also examined 47 bipolar affective patients and 62 control subjects for an association. Results: Six polymorphisms, R456H (1367G>A), G576S (1726G>A), H611R (1832A>G), I720V (2158A>G), E737K (2209G>A), and 2763G>A were detected. Four of the six were novel. No nonsense or frameshift mutation was detected. Genotypic and allelic distributions were similar between the depressive patients and the controls. No association with bipolar affective disorder was suggested. Limitations: Because of the small sample size, the probability of finding at least one patient with WFS-responsible mutation(s) was 70% if depression is associated with WFS1 mutation(s) in 5% of patients. Conclusion: It is not likely that WFS1 mutations are responsible for as much as 25% of depressive illness.