Department of Child Health, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Oman.
Pediatr Neurol. 2012 Feb;46(2):89-93. doi: 10.1016/j.pediatrneurol.2011.11.008.
Hyperekplexia is characterized by neonatal hypertonia and exaggerated startle reflex in response to loud noise or tactile stimuli. Mutations in patients with hyperekplexia were evident in several genes encoding proteins involved in glycinergic neurotransmission, i.e., glycine receptor α and β subunits, collybistin, gephyrin, and glycine transporter 2. We clinically and genetically characterized two large, unrelated consanguineous families with hyperekplexia. Affected members of the two families manifested hyperekplexia with mild mental retardation. Patients exhibited a novel homozygote c.593G>C missense mutation in GLRA1, resulting in amino acid substitution p.W170S in the corresponding mature glycine receptor α1 subunit. This mutation was absent in 400 randomly selected chromosomes in the same population. In conclusion, a novel p.W170S mutation in the extracellular ligand binding domain of glycine receptor α1 subunit was detected in patients with hyperekplexia and mild mental retardation.
发作性全身过度紧张症的特征是新生儿出现张力亢进，对巨大声响或触觉刺激反应过度。在发作性全身过度紧张症患者中，几种参与甘氨酸能神经传递的蛋白编码基因的突变是明显的，即甘氨酸受体α和β亚单位、脑桥蛋白、γ-氨基丁酸受体相关蛋白和甘氨酸转运体 2。我们对两个有发作性全身过度紧张症的大型、非相关近亲家系进行了临床和遗传学特征分析。两个家系的受累成员均表现为发作性全身过度紧张症伴轻度智力迟钝。患者在 GLRA1 中表现出一种新的纯合子 c.593G>C 错义突变，导致相应成熟甘氨酸受体 α1 亚单位的氨基酸取代 p.W170S。在同一人群的 400 个随机选择的染色体中，未检测到该突变。总之，在发作性全身过度紧张症伴轻度智力迟钝患者中检测到甘氨酸受体 α1 亚单位细胞外配体结合域的一种新的 p.W170S 突变。
