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偏头痛和癫痫的染色体 14q12-q23 和 12q24.2-q24.3 上的共享基因座。

Shared loci for migraine and epilepsy on chromosomes 14q12-q23 and 12q24.2-q24.3.

机构信息

Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.

出版信息

Neurology. 2012 Jan 17;78(3):202-9. doi: 10.1212/WNL.0b013e31823fcd87. Epub 2012 Jan 4.

Abstract

OBJECTIVES

To describe clinical characteristics and to identify susceptibility loci for epilepsy and migraine in a Finnish family with a complex phenotype.

METHODS

Participating family members were interviewed and medical files were reviewed. The seizure classification was made according to International League Against Epilepsy criteria. Migraine diagnosis was made using the validated Finnish Migraine Specific Questionnaire for Family Studies and criteria according to the current International Classification of Headache Disorders-II. DNA samples were obtained from 56 family members and nonparametric genome-wide linkage analyses were performed using 382 polymorphic microsatellite markers. The most promising loci were fine-mapped with additional microsatellite markers.

RESULTS

Clinical data were obtained from 60 family members of whom 12 (20%) had idiopathic epileptic seizures. Eight of those 12 (67%) also had migraine. Altogether 33 of the 60 family members (55%) had migraine. Significant evidence of linkage was found between a locus on 14q12-q23 and migraine (p = 0.0001). Suggestive evidence of linkage in this region was also found for epilepsy with generalized tonic-clonic seizures (p = 0.0034). In addition, significant evidence of linkage was found at a locus on 12q24.2-q24.3 (p < 0.001) for migraine alone and for the combined phenotype of migraine and epilepsy.

CONCLUSIONS

Our data suggest the occurrence of common susceptibility loci for epilepsy and migraine on chromosomes 14q12-q23 and 12q24.2-q24.3, implicating a shared genetic etiology for these 2 diseases.

摘要

目的

描述一个具有复杂表型的芬兰家族中癫痫和偏头痛的临床特征,并确定其易感基因座。

方法

对参与研究的家族成员进行访谈并查阅病历。根据国际抗癫痫联盟的标准对癫痫发作进行分类。偏头痛的诊断采用经验证的芬兰偏头痛特定家庭研究问卷和当前国际头痛疾病分类第二版的标准进行。从 56 名家族成员中获取 DNA 样本,并使用 382 个多态微卫星标记进行非参数全基因组连锁分析。对最有希望的基因座进行精细映射,使用额外的微卫星标记。

结果

从 60 名家族成员中获得了临床数据,其中 12 名(20%)患有特发性癫痫发作。这 12 名患者中有 8 名(67%)也患有偏头痛。总共 60 名家族成员中有 33 名(55%)患有偏头痛。在 14q12-q23 染色体上的一个基因座与偏头痛之间发现了显著的连锁证据(p = 0.0001)。在该区域还发现了与全身性强直阵挛性癫痫发作相关的连锁证据(p = 0.0034)。此外,在 12q24.2-q24.3 染色体上的一个基因座上也发现了与偏头痛(p < 0.001)和偏头痛与癫痫的综合表型相关的连锁证据。

结论

我们的数据表明,癫痫和偏头痛的共同易感基因座位于 14q12-q23 和 12q24.2-q24.3 染色体上,提示这两种疾病具有共同的遗传病因。

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