MUTATIONS IN THE ALPHA-1 SUBUNIT OF THE INHIBITORY GLYCINE RECEPTOR CAUSE THE DOMINANT NEUROLOGIC DISORDER, HYPEREKPLEXIA
MUTATIONS IN THE ALPHA-1 SUBUNIT OF THE INHIBITORY GLYCINE RECEPTOR CAUSE THE DOMINANT NEUROLOGIC DISORDER, HYPEREKPLEXIA
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DOI：
10.1038/ng1293-351
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发表时间：
1993-12-01
期刊：
影响因子：
30.8
通讯作者：
WASMUTH, JJ
中科院分区：
文献类型：
--
作者：
SHIANG, R;RYAN, SG;WASMUTH, JJ
遗传性高丛性或熟悉性惊吓病（STHE）是一种常染色体显性遗传的神经系统疾病，其特征在于中枢神经系统起源的显著肌肉僵硬和对意外的声音或触觉刺激的过度惊吓反应。在几个大家庭中的连锁分析提供了位点同质性的证据，并显示疾病基因与5号染色体长臂上的DNA标记连锁。在这里，我们描述了来自四个不同家族的STHE患者中编码甘氨酸受体α（1）亚基（GLRA 1）的基因中的点突变的鉴定。所有突变都发生在外显子6的相同碱基对中，并导致成熟蛋白质中不带电荷的氨基酸（亮氨酸或谷氨酰胺）取代Arg271。
Hereditary hyperekplexia, or familiar startle disease (STHE), is an autosomal dominant neurologic disorder characterized by marked muscle rigidity of central nervous system origin and an exaggerated startle response to unexpected acoustic or tactile stimuli. Linkage analyses in several large families provided evidence for locus homogeneity and showed the disease gene was linked to DNA markers on the long arm of chromosome 5. Here we describe the identification of point mutations in the gene encoding the alpha(1) subunit of the glycine receptor (GLRA1) in STHE patients from four different families. All mutations occur in the same base pair of exon 6 and result in the substitution of an uncharged amino acid (leucine or glutamine) for Arg271 in the mature protein.