ANALYSIS OF THE GENOMIC STRUCTURE OF THE HUMAN GLYCINE RECEPTOR ALPHA-2 SUBUNIT GENE AND EXCLUSION OF THIS GENE AS A CANDIDATE FOR RETT-SYNDROME

The gene that encodes the human alpha 2 subunit of the inhibitory glyc ine receptor (GLRA2) is located on the X chromosome (Xp22.2) in a cand idate region for a number of neurological disorders, Recently, an excl usion mapping strategy identified this region to be concordant in fami lial Rett syndrome (RTT) patients. Based on its established expression pattern and known function, GLRA2 was selected as a candidate gene fo r Rett syndrome. Major gene rearrangements were excluded based on Sout hern analysis using the GLRA2 cDNA as probe, To identify more subtle m utations, we determined the genomic structure for GLRA2, which consist s of nine exons and a putative alternatively spliced exon 3, The exon- intron boundaries were sequenced in order to design primer sets for po lymerase chain reaction (PCR) amplification of all exons and their imm ediately flanking intronic regions, PCR products amplified from genomi c DNA isolated from 40 RTT patients were subsequently characterized by heteroduplex analysis, and no mutations were detected. Characterizati on of the intron-exon structure of GLRA2 will facilitate future mutati onal analysis of this gene for other neurological disorders mapping to human Xp22.2, Am. J. Med. Genet. 78:176-178, 1998, (C) 1998 Wiley-Lis s, Inc.