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Original Paper

Free Access

A Rare Variant in CACNA1D Segregates with 7 Bipolar I Disorder Cases in a Large Pedigree

Ross J.a · Gedvilaite E.b · Badner J.A.d · Erdman C.a · Baird L.e · Matsunami N.e · Leppert M.e · Xing J.b, c · Byerley W.a

Author affiliations

aDepartment of Psychiatry, University of California, San Francisco, Calif., bDepartment of Genetics and cHuman Genetics Institute of New Jersey, Rutgers, the State University of New Jersey, New Brunswick, N.J., dDepartment of Psychiatry, University of Chicago, Chicago, Ill., and eDepartment of Human Genetics, University of Utah, Salt Lake City, Utah, USA

Corresponding Author

William Byerley, MD

401 Parnassus

University of California, San Francisco

San Francisco, CA 94143 (USA)

E-Mail william.byerley@ucsf.edu

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Whole-genome sequencing was performed on 3 bipolar I disorder (BPI) cases from a multiplex pedigree of European ancestry with 7 BPI cases. Within CACNA1D, a gene implicated by genome-wide association studies, a G to C nucleotide transversion at 53,835,340 base pairs (bps) was found predicting the substitution of proline for alanine at amino acid position 1751 (A1751P). Using Sanger sequencing, the DNA variant was shown to co-segregate with the remaining 4 BPI cases within the pedigree. A high-resolution DNA denaturing curve method was then used to screen for the presence of the A1751P change in 4,150 BPI cases from the NIMH Genetics Initiative. The A1751P variant was found in 4 BPI cases. A second variant within exon 43, a C to T nucleotide transition, was found in 1 case at 53,835,355 bps, predicting the substitution of tryptophan for arginine at amino acid position 1771 (R1771W). In the NHLBI Exome Sequencing Project database, the heterozygous A1751P variant was present in 3 of 4,300 subjects of European ancestry, and the R1771W change was not present in any subject. Given the rarity of these variants, large-scale case/control rare variant sequencing studies will be required for definitive conclusions.

© 2016 S. Karger AG, Basel

Article / Publication Details

Received: February 02, 2015
Accepted: June 28, 2016
Published online: August 03, 2016
Issue release date: October 2016

Number of Print Pages: 6
Number of Figures: 1
Number of Tables: 0

ISSN: 2296-9209 (Print)
eISSN: 2296-9179 (Online)

For additional information: http://www.karger.com/MNP

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