Early-onset progressive ataxia associated with the first CACNA1A mutation identified within the I-II loop
Early-onset progressive ataxia associated with the first CACNA1A mutation identified within the I-II loop
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DOI：
10.1016/j.jns.2007.01.008
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发表时间：
2007-03-15
影响因子：
4.4
通讯作者：
Casali, C.
中科院分区：
文献类型：
--
作者：
Cricchi, F.;Di Lorenzo, C.;Casali, C.
家族性偏瘫性偏头痛 1 型、脊髓小脑性共济失调 6 型 (SCA6) 和阵发性共济失调 2 型 (EA2) 是与 CACNAIA 基因突变相关的等位基因疾病，该基因编码 P/Q 型钙通道 (Ca(V)2.1) 的 α1 亚基。SCA6 和 EA2 具有许多共同的临床特征，例如突出的小脑受累和对药物反应良好的反应。乙酰唑胺治疗。然而，SCA6 发展为迟发性进行性共济失调，而 EA2 则发病较早且偶发。我们报告了两姐妹具有异质的临床表型。第一个患者在 30 岁后出现进行性小脑性共济失调，但没有明显的眩晕或头痛发作。乙酰唑胺为期一年的试验没有产生显着的结果。另一位报告称，自儿童晚期以来，曾出现眩晕、头痛和步态不平衡，对乙酰唑胺反应良好，随后出现中度慢性小脑性共济失调。脑 MRI 显示两名患者的小脑萎缩，尤其是蚓部。CACNAIA 的直接测序鉴定出外显子 11 中的杂合 1360G > A 突变，导致残基 454 (p.Ala454Thr) 处丙氨酸取代苏氨酸。这是对与临床表型相关的细胞质 I-II 环中的变化的首次描述。 (c) 2007 Elsevier B.V. 保留所有权利。
Familial hemiplegic migraine type 1, spinocerebellar ataxia type 6 (SCA6) and episodic ataxia type 2 (EA2) are allelic disorders associated with mutations in the CACNAIA gene, which encodes the alpha 1 subunit of the P/Q-type calcium channel (Ca(V)2.1).SCA6 and EA2 share a number of clinical features, such as prominent cerebellar involvement and good response to acetazolamide therapy. However, while SCA6 develops as a late-onset, progressive ataxia, EA2 has an earlier, and episodic, onset.We report on two sisters with a heterogeneous clinical phenotype. The first developed progressive cerebellar ataxia after age 30, without noticeable episodes of vertigo or headache. A 1 year trial with acetazolamide did not produce significant results. The other reported episodes of vertigo, headache and gait imbalance since late childhood, with good response to acetazolamide, before developing moderate chronic cerebellar ataxia. Brain MRI showed cerebellar atrophy, especially in the vermis, in both patients.Direct sequencing of CACNAIA identified a heterozygous 1360G > A mutation in exon 11 resulting in the substitution of alanine for threonine at residue 454 (p.Ala454Thr). This is the first description of a change residing in the cytoplasmic I-II loop associated with a clinical phenotype. (c) 2007 Elsevier B.V. All rights reserved.