Characterization of the human glutamate receptor subunit 3 gene (GRIA3), acandidate for bipolar disorder and nonspecific X-linked mental retardation

The X-chromosome breakpoint in a female patient with a balanced translocati on t(X;12)(q24;q15), bipolar affective disorder and mental retardation was mapped within the glutamate receptor 3 (GRIA3) gene by fluorescence in situ hybridization. The GRIA3 cDNA of 5894 bp was cloned, and the gene structur e and pattern of expression were determined. The most abundant GRIA3 transc ript is composed of 17 exons, An. additional 5 exons (2a, 2b, 5a, 5b, and 5 c) from the 5' end of the GRIA3 open reading frame were identified by EST a nalysis (ESTs AI379066 and AA947914), Two new polymorphic microsatellite re peats, (TC)(n=12-26) and (AC)(n=15-19) were identified within GRIA3 5' and 3'UTRs. No mutations were detected in families segregating disorders mappin g across GRIA3, one with X-linked bipolar affective disorder (BP) and one w ith a nonspecific X-linked mental retardation (MRX27). To assess the possib ility of the involvement of the GRIA3 gene in familial cases of complex BP, a large set of 373 individuals from 40 pedigrees segregating BP were genot yped using closely linked (DXS1001) and intragenic (DXS1212 and GRIA3 3' UT R (AC)(n))) GRIA3 STR markers. No evidence of linkage was found by parametr ic Lod score analysis (the highest Lod score was 0.3 at DXS1212, using the dominant transmission model) or by affected sib-pair analysis. (C) 1999 Aca demic Press.