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Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype


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.

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We thank our patient and family collaborators, Drs Gabriella Cora-Locatelli, Margaret Altemus, Theresa Pigott, Catherine Stayer, Joshua Rosenthal plus Diane Kazuba, Lucy Justement, Su-Jan Huang, Liz Maxwell, Julie Guroff, Teresa Tolliver and Theresa B DeGuzman for their contributions to this study, and Drs Klaus-Peter Lesch, Judith Rapoport and Sevilla Detera-Wadleigh for helpful suggestions with the manuscript. During the early stages of this work, Dr Norio Ozaki was supported at the NIAAA and NIMH Intramural Programs by Research Grants (10670923, 13470198, 13877152) from the Ministry of Science Education and Culture of Japan, the Research Grant for Nervous and Mental Disorders from the Ministry of Health and Welfare of Japan, and Special Coordination Funds for Promoting Science and Technology Target-oriented Brain Science Research Program from the Ministry of Science and Technology of Japan.

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Correspondence to D L Murphy.

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Ozaki, N., Goldman, D., Kaye, W. et al. Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype. Mol Psychiatry 8, 933–936 (2003).

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  • genetics
  • obsessive-compulsive disorder
  • autism
  • anorexia
  • constitutive activation

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