Locus for Familial Migrainous Vertigo Disease Maps to Chromosome 5q35
Locus for Familial Migrainous Vertigo Disease Maps to Chromosome 5q35
复制标题
DOI：
10.1177/000348940911800912
复制
发表时间：
2009-09-01
影响因子：
1.4
通讯作者：
Seidman, Jonathan G.
中科院分区：
文献类型：
--
作者：
Bahmad, Fayez, Jr.;DePalma, Steven R.;Seidman, Jonathan G.
目的：偏头痛性眩晕（与偏头痛相关的阵发性眩晕）有时作为常染色体显性遗传。然而，尚未报道疾病基因或可能负责的位点。我们试图绘制一个 4 代家族中家族性偏头痛眩晕的遗传位点，并确定该家族的疾病进展。方法：我们研究了一个偏头痛眩晕作为常染色体显性遗传的家族中的 23 名成员。获得的临床信息包括病例史以及耳鼻喉科、神经学、听力测定和影像学评估的结果。使用 Affymetrix Genechip Human Mapping 10K 微阵列进行全基因组连锁分析。使用微卫星标记对家庭成员的 DNA 进行基因分型，以进一步评估全基因组扫描中确定的候选位点。结果：23 名家庭成员中，有 10 人在 35 岁后开始患有偏头痛性眩晕。偏头痛通常在眩晕发作前 15 至 20 年出现。超过 12 年的纵向听力测试显示，稳定的高频感音神经性听力损失与老年性耳聋相符。没有观察到低频或波动性听力损失。前庭测试和影像学检查结果未见异常。遗传分析确定了染色体 5q35 上包含疾病基因的位点 rs244895 和 D5S2073 之间的 12.0 MB 间隔（优势得分的对数，4.21）。结论：我们报告了家族性偏头痛性眩晕的第一个位点，该位点映射到 5q35。
Objectives: Migrainous vertigo (episodic vertigo associated with migraine) is sometimes inherited as an autosomal dominant trait. However, neither disease genes nor loci that might be responsible have been reported. We sought to map the genetic locus for familial migrainous vertigo in a 4-generation family and to define the progression of disease in this family.Methods: We studied 23 members in a family in whom migrainous vertigo was inherited as an autosomal dominant trait. Clinical information obtained included case histories and results of otolaryngological, neurologic, audiometric, and imaging evaluations. Genome-wide linkage analysis was performed with Affymetrix Genechip Human Mapping 10K microarrays. Genotyping of family members' DNA with microsatellite markers was used to further assess candidate loci identified from the whole-genome scan.Results: Of 23 family members, 10 suffered from migrainous vertigo beginning after 35 years of age. Migraine head aches usually preceded the onset of vertigo by 15 to 20 years. Longitudinal audiometric Studies over 12 years showed stable, high-frequency sensorineural hearing loss consistent with presbycusis. Low-frequency or fluctuating hearing loss was not observed. The results of vestibular testing and imaging Studies were unremarkable. Genetic analysis defined a 12.0 MB interval on chromosome 5q35 between loci rs244895 and D5S2073 that contained the disease gene (logarithm of odds score, 4.21).Conclusions: We report the first locus for familial migrainous vertigo, which mapped to 5q35.