Brune W, Weber R G, Saul B, von Knebel Doeberitz M, Grond-Ginsbach C, Kellerman K, Meinck H M, Becker C M
Zentrum für Molekulare Biologie, Universität Heidelberg, Germany.
Am J Hum Genet. 1996 May;58(5):989-97.
Dominant missense mutations in the human glycine receptor (GlyR) alpha 1 subunit gene (GLRA1) give rise to hereditary hyperekplexia. These mutations impair agonist affinities and change conductance states of expressed mutant channels, resulting in a partial loss of function. In a recessive case of hyperekplexia, we found a deletion of exons 1-6 of the GLRA1 gene. Born to consanguineous parents, the affected child is homozygous for this GLRA1(null) allele consistent with a complete loss of gene function. The child displayed exaggerated startle responses and pronounced head-retraction jerks reflecting a disinhibition of vestigial brain-stem reflexes. In contrast, proprio- and exteroceptive inhibition of muscle activity previously correlated to glycinergic mechanisms were not affected. This case demonstrates that, in contrast to the lethal effect of a null allele in the recessive mouse mutant oscillator (Glra1 spd-ot), the loss of the GlyR alpha 1 subunit is effectively compensated in man.
人类甘氨酸受体（GlyR）α1亚基基因（GLRA1）中的显性错义突变会导致遗传性易惊症。这些突变会损害激动剂亲和力并改变表达的突变通道的电导状态，从而导致功能部分丧失。在一例隐性易惊症病例中，我们发现GLRA1基因的外显子1 - 6缺失。患儿父母为近亲结婚，该患儿对于此GLRA1（无效）等位基因呈纯合状态，这与基因功能的完全丧失相符。该患儿表现出夸张的惊吓反应和明显的头部回缩抽搐，反映出残留脑干反射的去抑制状态。相比之下，先前与甘氨酸能机制相关的肌肉活动的本体感受和外感受抑制并未受到影响。该病例表明，与隐性小鼠突变体振荡器（Glra1 spd-ot）中无效等位基因的致死效应相反，人类中甘氨酸受体α1亚基的缺失得到了有效补偿。
