The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel.
The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel.
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DOI：
10.1056/nejm200107053450103
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发表时间：
2001-07-01
影响因子：
158.5
通讯作者：
Tournier-Lasserve, E
中科院分区：
文献类型：
--
作者：
Ducros, A;Denier, C;Tournier-Lasserve, E
背景资料：家族性偏瘫型偏头痛是一种常染色体显性遗传疾病，其特征是短暂性轻偏瘫发作，随后发生偏头痛，可分为纯家族性偏瘫型偏头痛（影响80%的家族）和家族性偏瘫型偏头痛伴永久性小脑体征（影响20%的家族）。编码神经元钙通道的CACNA 1A突变存在于50%的偏瘫性偏头痛家族中，包括所有具有小脑体征的家族。我们研究了28个伴或不伴小脑体征的偏瘫型偏头痛家系中与CACNA 1A突变相关的各种临床表现。分析CACNA 1A，在16个受偏瘫型偏头痛和小脑体征影响的家族的15个先证者中检测到9个突变，在3个散发性偏瘫型偏头痛和小脑体征的受试者中检测到2个突变，12个纯偏瘫型偏头痛家系中有4个先证者存在偏头痛。先证者和亲属的基因分型确定了共117例突变的受试者，其临床表现进行了详细的assessment.Results：89%的突变的受试者有偏瘫性偏头痛的发作。三分之一的人有严重的昏迷，长期偏瘫，或两者兼而有之，完全康复。所有9个突变，包括5个新发现的突变，都是错义突变。六个突变与偏瘫性偏头痛和小脑体征相关，83%的这六个突变的受试者有眼球震颤，共济失调，或两者兼而有之。三个突变与单纯偏瘫性偏头痛有关。结论：CACNA 1A突变的偏瘫性偏头痛具有广泛的临床谱。这种临床变异性部分与各种类型的突变有关。（新英格兰医学杂志2001;345：17-24。）版权所有（C）2001马萨诸塞州医学会。
Background: Familial hemiplegic migraine, an autosomal dominant disorder characterized by attacks of transient hemiparesis followed by a migraine headache, is divided into pure familial hemiplegic migraine (affecting 80 percent of families) and familial hemiplegic migraine with permanent cerebellar signs (affecting 20 percent of families). Mutations in CACNA1A, which encodes a neuronal calcium channel, are present in 50 percent of families with hemiplegic migraine, including all those with cerebellar signs. We studied the various clinical manifestations associated with mutations in CACNA1A in 28 families with hemiplegic migraine with and without cerebellar signs.Methods: CACNA1A was analyzed and nine mutations were detected in 15 of 16 probands of families affected by hemiplegic migraine and cerebellar signs, in 2 of 3 subjects with sporadic hemiplegic migraine and cerebellar signs, and in 4 of 12 probands of families affected by pure hemiplegic migraine. Genotyping of probands and relatives identified a total of 117 subjects with mutations whose clinical manifestations were assessed in detail.Results: Eighty-nine percent of the subjects with mutations had attacks of hemiplegic migraine. One third had severe attacks with coma, prolonged hemiplegia, or both, with full recovery. All nine mutations, including five newly identified ones, were missense mutations. Six mutations were associated with hemiplegic migraine and cerebellar signs, and 83 percent of the subjects with these six mutations had nystagmus, ataxia, or both. Three mutations were associated with pure hemiplegic migraine.Conclusions: Hemiplegic migraine in subjects with mutations in CACNA1A has a broad clinical spectrum. This clinical variability is partially associated with the various types of mutations. (N Engl J Med 2001;345:17-24.) Copyright (C) 2001 Massachusetts Medical Society.