Hyperekplexia-like syndromes without mutations in the GLRA1 gene
Hyperekplexia-like syndromes without mutations in the GLRA1 gene
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DOI：
10.1016/s0303-8467(97)00022-x
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发表时间：
1997-08-01
影响因子：
1.9
通讯作者：
Frants, RR
中科院分区：
文献类型：
--
作者：
Vergouwe, MN;Tijssen, MAJ;Frants, RR
过度兴奋（MIM：149400）：或惊跳病，是一种常染色体显性神经系统疾病，其特征是出生后立即出现极端全身僵硬，在生命的最初几年内正常化。这种疾病的其他特征是对意外的，特别是听觉刺激的过度惊吓反应，以及短暂的全身僵硬，在此期间不可能进行自主运动。连锁分析将这种疾病的基因定位于染色体5 q33-q35。随后，编码甘氨酸受体α 1亚基的GLRA 1基因突变被证明与该疾病有因果关系。本研究对散发性患者及其父母进行了该基因全部外显子和南京内含子序列的突变分析。此外，筛选了具有非常严重受影响的个体的原始Dutch hyperekplexia家族的分支的GLRA 1基因中的额外突变。除了两个多态性（其中一个导致氨基酸改变）之外，在甘氨酸受体的α 1亚基中未发现潜在的致病突变，连同单倍型分析，这些结果排除了隐性遗传或新的突变病因在这些hyperklexia样综合征，并强调hyperklexia样综合征可以由其他遗传因素引起。尚未排除其他基因编码的功能性甘氨酸受体复合物的亚基的参与。(C)1997年Elsevier Science B.V.
Hyperekplexia (MIM: 149400): or startle disease, is an autosomal dominant neurological disorder characterized by an extreme generalized stiffness immediately after birth, normalizing during the first years of life. Other features of this disorder are excessive startle reactions to unexpected, particularly auditory, stimuli together with a short period of generalized stiffness during which voluntary movements are impossible. Linkage analysis mapped a gene for this disorder to chromosome 5q33-q35. Subsequently, mutations in the GLRA1 gene encoding the alpha 1-subunit of the glycine receptor proved to be causally related to the disease. In the present study, mutation analysis of all exon and nanking intron sequences of this gene was performed in sporadic patients and their parents. Moreover, a branch of the original Dutch hyperekplexia family with a very severely affected individual was screened for an additional mutation in the GLRA1 gene, Except for two polymorphisms, of which one results in an amino acid change, no potentially disease causing mutations were found in the alpha 1-subunit of the glycine receptor, Together with haplotype analysis these results exclude a recessive inheritance or new mutation etiology in these hyperekplexia-like syndromes and emphasize that hyperekplexia-like syndromes can be caused by other genetic factors. The involvement of other genes encoding subunits of the functional glycine receptor complex has not been excluded. (C) 1997 Elsevier Science B.V.