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 10% 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-Saharan Africa, India, China, and Sweden (n = 277).


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 hTPH2 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.
Human Genetics and Cognitive Functions, Pasteur Institute, Paris, France. delorme@im3.inserm.fr
Richard
R
Delorme
Christelle M
CM
Durand
Catalina
C
Betancur
Michael
M
Wagner
Stephan
S
Ruhrmann
Hans-Juergen
HJ
Grabe
Gudrun
G
Nygren
Christopher
C
Gillberg
Marion
M
Leboyer
Thomas
T
Bourgeron
Philippe
P
Courtet
Fabrice
F
Jollant
Catherine
C
Buresi
Jean-Michel
JM
Aubry
Patrick
P
Baud
Guido
G
Bondolfi
Gilles
G
Bertschy
Nader
N
Perroud
Alain
A
Malafosse
D000328:Adult; D000483:Alleles; D002875:Chromosomes / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014365:Tryptophan Hydroxylase / Q000235:genetics*
C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase