Autosomal dominant moyamoya disease maps to chromosome 17q25.3
Autosomal dominant moyamoya disease maps to chromosome 17q25.3
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DOI：
10.1212/01.wnl.0000291012.49986.f9
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发表时间：
2008-06-10
期刊：
影响因子：
9.9
通讯作者：
Koizumi, A.
中科院分区：
文献类型：
--
作者：
Mineharu, Y.;Liu, W.;Koizumi, A.
背景：烟雾病是一种特发性狭窄闭塞性脑血管疾病，是脑卒中的重要病因。然而，该病的病因在很大程度上仍是未知的。方法：我们以前发现烟雾病的遗传模式是常染色体显性的，不完全外显。在这里，我们报告了15个日本大家庭中烟雾病的全基因组参数连锁分析。我们在两种诊断分类下进行了联系分析：狭义和广义。由于该疾病的不完全和年龄依赖外显率，应用了仅受影响成员的分析。结果：在两种分类下，仅在染色体17q25.3上观察到显著的连锁证据，D17S704的多点对数（lod）分数最大值为6.57（狭义分类）和8.07（广义分类）。单倍型分析显示，除了一个家族外，所有家族中都存在一种疾病单倍型的分离，并且信息丰富的交叉使MMD位点定位到D17S1806和17q端粒之间的3.5 mb区域，包含94个注释基因。结论：本研究提示常染色体显性烟雾病的主要基因位点在染色体17q25.3上。
Background: Moyamoya disease (MMD) is an idiopathic steno-occlusive cerebrovascular disease that represents an important cause of stroke. However, etiology of the disease has remained largely unknown.Methods: We previously showed that the inheritance pattern of MMD is autosomal dominant with incomplete penetrance. Here, we report the genome-wide parametric linkage analysis for MMD in 15 extended Japanese families. We conducted linkage analyses under two diagnostic classifications: narrow and broad. Affected member-only analysis was applied due to incomplete and age-dependent penetrance of the disease.Results: Under both classifications, significant evidence of linkage was only observed on chromosome 17q25.3, with maximum multipoint logarithm of odds (lod) scores of 6.57 (under the narrow classification) and 8.07 (under the broad classification) at D17S704. Haplotype analysis revealed segregation of a disease haplotype in all families but one, and informative crossovers enabled mapping of the MMD locus to a 3.5-Mb region between D17S1806 and the telomere of 17q, encompassing 94 annotated genes.Conclusions: Our data suggest that there is a major gene locus for autosomal dominant moyamoya disease on chromosome 17q25.3.