Analysis of the genomic structure of the human glycine receptor alpha2 subunit gene and exclusion of this gene as a candidate for Rett syndrome.
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Cummings CJ, Dahle EJ, Zoghbi HY
Analysis of the genomic structure of the human glycine receptor alpha2 subunit gene and exclusion of this gene as a candidate for Rett syndrome.
Am J Med Genet. 1998 Jun 30;78(2):176-8.
- PubMed ID
- 9674912 [ View in PubMed]
- Abstract
The gene that encodes the human alpha2 subunit of the inhibitory glycine receptor (GLRA2) is located on the X chromosome (Xp22.2) in a candidate region for a number of neurological disorders. Recently, an exclusion mapping strategy identified this region to be concordant in familial Rett syndrome (RTT) patients. Based on its established expression pattern and known function, GLRA2 was selected as a candidate gene for Rett syndrome. Major gene rearrangements were excluded based on Southern analysis using the GLRA2 cDNA as probe. To identify more subtle mutations, we determined the genomic structure for GLRA2, which consists of nine exons and a putative alternatively spliced exon 3. The exon-intron boundaries were sequenced in order to design primer sets for polymerase chain reaction (PCR) amplification of all exons and their immediately flanking intronic regions. PCR products amplified from genomic DNA isolated from 40 RTT patients were subsequently characterized by heteroduplex analysis, and no mutations were detected. Characterization of the intron-exon structure of GLRA2 will facilitate future mutational analysis of this gene for other neurological disorders mapping to human Xp22.2.