No human tryptophan hydroxylase-2 gene R441H mutation in a large cohort of psychiatric patients and control subjects

Background: It was recently reported that a rare functional variant, R441H, in the human tryptophan hydroxylase-2 gene (hTPH2) could represent an important risk factor for unipolar major depression (UP) since it was originally found in 10916 of UP patients (vs. 1.4% in control subjects). Methods. We explored the occurrence of this variation in patients with affective disorders (n = 646), autism spectrum disorders (n = 224), and obsessive-compulsive disorder (OCD) (n = 201); in healthy volunteers with no psychiatric disorders (n = 246); and in an ethnic panel of control individuals from North Africa, Sub-Sabaran Africa, India, China, and Sweden (n = 2 77). Results: Surprisingly, we did not observe the R441H variant in any of the individuals screened (3188 independent chromosomes). Conclusions: Our results do not confirm the role of the R441H mutation of the bTPH2 gene in the susceptibility to UP. The absence of the variant from a large cohort of psychiatric patients and control subjects suggests that the findings reported in the original study could be due to a genotyping error or to stratification of the initial population reported. Additional data by other groups should contribute to the clarification of the discrepancy between our results and those previous published.