Missense CACNA1A mutation causing episodic ataxia type 2
Missense CACNA1A mutation causing episodic ataxia type 2
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DOI：
10.1001/archneur.58.2.292
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发表时间：
2001-02-01
影响因子：
--
通讯作者：
Tournier-Lasserve, E
中科院分区：
文献类型：
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作者：
Denier, C;Ducros, A;Tournier-Lasserve, E
目的：描述CACNA 1A突变的性质在以前未报道的家庭与发作性共济失调2型（EA 2）和更好地描绘EA 2的临床features.Background：发作性共济失调2型是一种常染色体显性遗传疾病的特点是乙酰唑胺反应性发作的小脑共济失调，通常在儿童或青春期开始复发。突变基因CACNA 1A位于19号染色体上，编码α 1A亚基电压依赖性钙通道。方法：采用单链构象多态性分析和测序分析相结合的方法，对CACNA 1A基因47个外显子进行突变检测，并对突变位点进行分析。结果：发现1个CACNA 1A错义突变（Glu 1757 Lys）。在200条对照染色体上均不存在。据预测，导致在一个高度保守的位置，在一个域，发挥了重要作用的功能的channel.Conclusions：谷氨酸1757赖氨酸错义突变可能是致病性的，导致发作性共济失调的家庭内的表型是无法区分的EA 2除了发病年龄稍晚。这些数据强烈表明，需要进一步的工作，以充分建立CACNA 1A突变的基因型/表型相关性。
Objectives: To characterize the nature of CACNA1A mutation in a previously unreported family with episodic ataxia type 2 (EA2) and to better delineate EA2 clinical features.Background: Episodic ataxia type 2 is an autosomal dominant disorder characterized by the recurrence of acetazolamide-responsive spells of cerebellar ataxia, usually starting during childhood or adolescence. The mutated gene, CACNA1A, is located on chromosome 19 and encodes the alpha 1A subunit voltage-dependent calcium channel. So far, most CACNA1A mutations detected in patients with EA2 have led to a truncated CACNA1A protein, whereas missense mutations cause familial hemiplegic migraine.Methods: All 47 exons of CACNA1A were screened by a combination of single-strand conformer polymorphism and sequencing analysis.Results: A CACNA1A missense mutation, Glu 1757 Lys, was identified. it was absent in 200 control chromosomes. it is predicted to result in an amino acid substitution at a highly phylogenetically conserved position, within a domain that plays a major role in the function of the channel.Conclusions: The Glu 1757 Lys missense mutation is likely to be pathogenic, causing episodic ataxia within a family whose phenotype is indistinguishable from EA2 except for a slightly later age of onset. These data strongly suggest that additional work is needed to fully establish genotype/phenotype correlations for CACNA1A mutations.