SYSTEMATIC SCREENING FOR MUTATIONS IN THE CODING REGION OF THE HUMAN SEROTONIN TRANSPORTER (5-HTT) GENE USING PCR AND DGGE

Dysfunctions in serotonergic pathways may underlie several psychiatric disorders. The reuptake of serotonin (5-HT) from synaptic terminals i s mediated by a specific transporter (5-HTT). Genetic variation in the gene coding for the 5-HTT protein might be involved in the predisposi tion to psychiatric disorders. A systematic screening of the whole cod ing sequence of the 5-HTT gene in mood disorder (MD) and obsessive-com pulsive disorder (OCD) patients, as well as in healthy controls, using PCR and denaturing gradient gel electrophoresis (DGGE) revealed the p resence of two mutations. The first was in intron 4, and the second wa s a C --> A transversion leading to an amino-acid exchange (Leu --> Me t) in position 255 of the deduced protein sequence. No further occurre nce of this substitution was found in an extended sample of patients a nd controls. Therefore, structural modifications of the 5-HTT gene do not seem to play either a major or minor role in the genetic predispos ition to MD or OCD. (C) 1996 Wiley-Liss, Inc.