Milani N, Mülhardt C, Weber R G, Lichter P, Kioschis P, Poustka A, Becker C M
Institut für Biochemie, Universität Erlangen-Nürnberg, Germany.
Genomics. 1998 Jun 15;50(3):341-5. doi: 10.1006/geno.1998.5324.
The glycine receptor of the human CNS comprises ligand-binding alpha 1 and structural beta subunits encoded by the GLRA1 and GLRB genes, respectively. Screening of a human hippocampal cDNA library resulted in the identification of the novel subunit transcript beta B, differing in the 5'-UTR. Analysis of the genomic organization of GLRB showed that the coding region is distributed over nine exons, highly homologous to the GLRA1 gene. By in situ hybridization, the chromosomal localization of GLRB was refined to band 4q31.3. Based on the identical phenotypes of mouse lines carrying mutant alleles of the alpha 1 and beta subunit genes, GLRB was assumed to be a candidate gene for those cases of hyperekplexia that cannot be associated with mutations of GLRA1. Therefore, flanking intronic sequences were determined, and DNA samples from more than 30 index patients were subjected to SSCP screening of the entire GLRB coding region. A polymorphism in exon 8 was found both in the normal population and in families affected by hyperekplexia, although no coding mutation was detectable.
人类中枢神经系统的甘氨酸受体由分别由GLRA1和GLRB基因编码的配体结合α1亚基和结构β亚基组成。对人海马cDNA文库的筛选导致鉴定出新型亚基转录本βB，其5'-UTR存在差异。对GLRB基因组织结构的分析表明，编码区分布在9个外显子上，与GLRA1基因高度同源。通过原位杂交，将GLRB的染色体定位精确到4q31.3带。基于携带α1和β亚基基因突变等位基因的小鼠品系具有相同的表型，推测GLRB是那些与GLRA1突变无关的惊跳症病例的候选基因。因此，确定了侧翼内含子序列，并对30多名索引患者的DNA样本进行了GLRB编码区的单链构象多态性（SSCP）筛选。尽管未检测到编码突变，但在正常人群和受惊跳症影响的家庭中均发现外显子8存在多态性。
