Shiang R, Ryan S G, Zhu Y Z, Fielder T J, Allen R J, Fryer A, Yamashita S, O'Connell P, Wasmuth J J
Department of Biological Chemistry, University of California, Irvine 92717, USA.
Ann Neurol. 1995 Jul;38(1):85-91. doi: 10.1002/ana.410380115.
Hyperekplexia is a rare, autosomal dominant neurological disorder characterized by hypertonia, especially in infancy, and by an exaggerated startle response. This disorder is caused by mutations in the alpha 1 subunit of the inhibitory glycine receptor (GLRA1). We previously reported two GLRA1 point mutations detected in 4 unrelated hyperekplexia families; both mutations were at nucleotide 1192 and resulted in the replacement of Arg271 by a glutamine (R271Q) in one case and a leucine (R271L) in the other. Here, 5 additional hyperekplexia families are shown to have the most common G-to-A transition mutation at nucleotide 1192. Haplotype analysis using polymorphisms within and close to the GLRA1 locus suggests that this mutation has arisen at least twice (and possibly four times). In 2 additional families, a third mutation is also presented that changes a tyrosine at amino acid 279 to a cysteine (Y279C). Five patients with atypical clinical features and equivocal or absent family history of hyperekplexia and 1 patient with a classical presentation but not family history are presented in whom a mutation in the GLRA1 gene was not detected. Thus, only clinically typical hyperekplexia appears to be consistently associated with GLRA1 mutations, and these affect a specific extracellular domain of the protein.
惊跳症是一种罕见的常染色体显性神经疾病，其特征为张力亢进，尤其是在婴儿期，以及夸张的惊吓反应。这种疾病是由抑制性甘氨酸受体（GLRA1）的α1亚基突变引起的。我们之前报道了在4个无亲缘关系的惊跳症家族中检测到的两个GLRA1点突变；两个突变均位于核苷酸1192处，其中一例导致精氨酸271被谷氨酰胺取代（R271Q），另一例被亮氨酸取代（R271L）。在此，另外5个惊跳症家族被证明在核苷酸1192处存在最常见的G到A转换突变。使用GLRA1基因座内及附近的多态性进行单倍型分析表明，该突变至少出现了两次（可能为四次）。在另外2个家族中，还发现了第三个突变，该突变将氨基酸279处的酪氨酸变为半胱氨酸（Y279C）。本文报告了5例具有非典型临床特征且惊跳症家族史不明确或无家族史的患者，以及1例具有典型表现但无家族史的患者，在这些患者中未检测到GLRA1基因突变。因此，似乎只有临床典型的惊跳症与GLRA1突变始终相关，并且这些突变影响该蛋白的一个特定细胞外结构域。
