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Screening of PIP5K2A promoter region for mutations in bipolar disorder and schizophrenia

Stopkova, Pavlaa; Vevera, Janb; Paclt, Ivob; Zukov, Iljab; Papolos, Demitri F.a; Saito, Takuyaa; Lachman, Herbert M.a


Objective To analyze the promoter region of PIP5K2A, a phosphatidylinositol 4-phosphate 5-kinase that maps to 10p in a region linked to both bipolar disorder and schizophrenia.

Methods The promoter region was screened by single-strand conformation polymorphism analysis and DNA sequencing. Allele frequencies were determined in a case–control study. Functional significance of a promoter variant was determined by electromobility gel shift assays.

Results Homozygosity for a rare putative promoter variant, −1007C→T, was found in only two patients with schizophrenia and in no controls or bipolar patients. The variant forms a 7/8 base match for the binding site of Oct-1, a member of the POU homeodomain family. Electromobility gel shift assays revealed increased binding of a brain-specific nuclear protein to the −1007T allele compared with −1007C.

Conclusion The data suggest that homozygosity for −1007T could be a rare genetic factor in the development of schizophrenia.

aDepartment of Psychiatry and Behavioral Sciences, Division of Psychiatry Research, Albert Einstein College of Medicine, Bronx, New York, USA

bPsychiatric Clinic, First Medical Faculty, Charles University, Prague, Czech Republic

Sponsorships: H.M.L. and D.F.P. are recipients of NARSAD Independent Investigator Awards and a grant from the Juvenile Bipolar Disorder Foundation. I.P., I.Z. and J.V. are supported by a research grant from the Ministry of Education and Youth, MSM111100001, Czech Republic.

Correspondence and requests for reprints to Herbert M. Lachman, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA

Tel: 718 430 2428; fax: 718 430 8772;


Accepted 13 October 2004

© 2005 Lippincott Williams & Wilkins, Inc.