Compound heterozygosity and nonsense mutations in the α1-subunit of the inhibitory glycine receptor in hyperekplexia
Compound heterozygosity and nonsense mutations in the α1-subunit of the inhibitory glycine receptor in hyperekplexia
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DOI：
10.1007/s004390100569
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发表时间：
2001-09-01
期刊：
影响因子：
5.3
通讯作者：
Owen, MJ
中科院分区：
文献类型：
--
作者：
Rees, MI;Lewis, TM;Owen, MJ
α（1）抑制性甘氨酸受体是一种配体门控氯离子通道，由三个配体结合α（1）亚基和两个结构β亚基组成，聚集在抑制性甘氨酸能神经元的突触后膜上。GLRA 1亚基的显性和隐性突变与一部分患有惊吓疾病或过度兴奋的个体和家族相关（MIM：149400）。在对22名患有hyperklexia和hyperklexia相关疾病的无关个体进行SSCP和双向双脱氧指纹突变分析后，我们进一步报告了GLRA1中的新错义突变和第一个无义点突变，其中大多数位于先前与显性疾病分离突变相关的区域之外。人群研究揭示了每个突变与疾病的独特关联，并揭示了一部分散发性hyperekplexia是由隐性GLRA1突变的纯合遗传或作为复合杂合子的一部分。
The alpha (1)-inhibitory glycine receptor is a ligand-gated chloride channel composed of three ligand-binding alpha (1)-subunits and two structural beta -subunits that are clustered on the postsynaptic membrane of inhibitory glycinergic neurons. Dominant and recessive mutations in GLRA1 subunits have been associated with a proportion of individuals and families with startle disease or hyperekplexia (MIM: 149400). Following SSCP and bi-directional dideoxy fingerprinting mutational analysis of 22 unrelated individuals with hyperekplexia and hyperekplexia-related conditions, we report further novel missense mutations and the first nonsense point mutations in GLRA1, the majority of which localise outside the regions previously associated with dominant, disease-segregating mutations. Population studies reveal the unique association of each mutation with disease, and reveals that a proportion of sporadic hyperekplexia is accounted for by the homozygous inheritance of recessive GLRA1 mutations or as part of a compound heterozygote.