THE HUMAN SEROTONIN 7(5-HT7) RECEPTOR GENE - GENOMIC ORGANIZATION ANDSYSTEMATIC MUTATION SCREENING IN SCHIZOPHRENIA AND BIPOLAR AFFECTIVE-DISORDER

In the present study, we evaluated the possible contribution of geneti c variation of the serotonin 5-HT7 receptor to the development of schi zophrenia and bipolar affective disorder. Cloning and characterization of exon-flanking intronic sequences enabled us to investigate the who le coding region and the exon-intron boundaries of the human 5-HT7 rec eptor gene. Using single-strand conformational analysis, we screened f or presence of DNA sequence variation in a sample of 137 unrelated ind ividuals including 45 schizophrenic and 46 bipolar affective patients, as well as 46 healthy controls. We detected two rare naturally occurr ing receptor variants (Pro-279-Leu, Thr-92-Lys) and a silent nucleotid e substitution (A-->G) at position +1233. The occurrence of the Pro-27 9-Leu and Thr-92-Lys substitutions was studied in an extended sample o f patients (n = 462) and controls (n = 335). The Leu-279 variant was f ound in similar frequency in all groups, indicating that presence of t his variant is not causally related to the development of schizophreni a or bipolar affective disorder. The Lys-92 variant was found in a sin gle individual who suffered from bipolar affective disorder. Investiga tion of the patient's family revealed independent segregation between the Lys-92 variant and psychiatric illness. Our data suggests that gen etic variation of the 5-HT7 receptor does not play a major role in the development of bipolar affective disorder and schizophrenia.