Folkhälsan Research Center, Biomedicum Helsinki, PO Box 63, 00014 University of Helsinki, Finland.
Neurology. 2010 Apr 13;74(15):1171-7. doi: 10.1212/WNL.0b013e3181d8ffcb.
To identify susceptibility loci for visual migraine aura in migraine families primarily affected with scintillating scotoma type of aura.
We included Finnish migraine families with at least 2 affected family members with scintillating scotoma as defined by the International Criteria for Headache Disorders-II. A total of 36 multigenerational families containing 351 individuals were included, 185 of whom have visual aura and 159 have scintillating scotoma. Parametric and nonparametric linkage analyses were performed with 378 microsatellite markers. The most promising linkage loci found were fine-mapped with additional microsatellite markers.
A novel locus on chromosome 9q22-q31 for migraine aura was identified (HLOD = 4.7 at 104 cM). Fine-mapping identified a shared haplotype segment of 12 cM (9.8 Mb) on 9q21-q22 among the aura affected. Four other loci showed linkage to aura: a locus on 12p13 showed significant evidence of linkage, and suggestive evidence of linkage was detected to loci on chromosomes 5q13, 6q25, and 13q14.
A novel visual migraine aura locus has been mapped to chromosome 9q21-q22. Interestingly, this region has previously been linked to occipitotemporal lobe epilepsy with prominent visual symptoms. Our finding further supports a shared genetic background in migraine and epilepsy and suggests that susceptibility variant(s) to visual aura for both of these traits are located in the 9q21-q22 locus.
鉴定主要受闪烁暗点型先兆影响的偏头痛家系中视觉偏头痛先兆的易感基因座。
我们纳入了至少有 2 名符合国际头痛疾病分类标准-II 定义的闪烁暗点型先兆的偏头痛芬兰家系。共纳入 36 个包含 351 名个体的多代家族,其中 185 名有视觉先兆,159 名有闪烁暗点。采用 378 个微卫星标记进行参数和非参数连锁分析。发现最有希望的连锁部位后,用额外的微卫星标记进行精细定位。
在染色体 9q22-q31 上发现了一个新的偏头痛先兆易感基因座(104cM 处的 HLOD=4.7)。精细定位确定了受先兆影响的个体在 9q21-q22 上共享的 12cM(9.8Mb)单倍型片段。另外 4 个部位显示与先兆有连锁关系:12p13 上的一个部位显示出显著的连锁证据,染色体 5q13、6q25 和 13q14 上的连锁证据也有提示意义。
已将一个新的视觉偏头痛先兆基因座定位到染色体 9q21-q22。有趣的是,该区域先前与以显著视觉症状为特征的枕颞叶癫痫有关。我们的发现进一步支持偏头痛和癫痫之间存在共同的遗传背景,并表明这两种疾病的视觉先兆的易感性变异位于 9q21-q22 基因座。