1. ¹Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
2. ²Laboratory of Neurogenetics, NIAAA, NIH, Rockville, MD, USA
3. ³Department of Psychiatry, University of Pittsburgh Medical Center, Western Psychiatric Institute & Clinic, Iroquois Building, Pittsburgh, PA, USA
4. ⁴Butler Hospital, Providence, RI, USA
5. ⁵Department of Psychiatry, Brown University School of Medicine, USA
6. ⁶Yale University School of Medicine, VA Connecticut Healthcare System, Psychiatry 116A2, West Haven, CT, USA
7. ⁷Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA
8. ⁸Laboratory of Clinical Science, MSC 1264, NIMH, NIH, Bethesda, MD, USA

Correspondence: Dr DL Murphy, Laboratory of Clinical Science, Building 10, Room 3D41, MSC 1264, 10 Center Drive, NIMH, NIH, Bethesda, MD 20892-1264, USA. E-mail: dm30h@nih.gov

Received 29 January 2003; Revised 7 April 2003; Accepted 16 April 2003.

Abstract

Two common serotonin transporter (SERT) untranslated region gene variants have been intensively studied, but remain inconclusively linked to depression and other neuropsychiatric disorders. We now report an uncommon coding region SERT mutation, Ile425Val, in two unrelated families with OCD and other serotonin-related disorders. Six of the seven family members with this mutation had OCD (n=5) or obsessive-compulsive personality disorder (n=1) and some also met diagnostic criteria for multiple other disorders (Asperger's syndrome, social phobia, anorexia nervosa, tic disorder and alcohol and other substance abuse/dependence). The four most clinically affected individuals—the two probands and their two slbs—had the I425V SERT gene gain-of-function mutation and were also homozygous for 5'-UTR SERT gene variant with greater transcriptional efficacy.