Mapping of a first locus for autosomal dominant myxomatous mitral-valve prolapse to chromosome 16p11.2-p12.1
Mapping of a first locus for autosomal dominant myxomatous mitral-valve prolapse to chromosome 16p11.2-p12.1
复制标题
DOI：
10.1086/302624
复制
发表时间：
1999-11-01
影响因子：
9.8
通讯作者：
Jeunemaitre, X
中科院分区：
文献类型：
--
作者：
Disse, S;Abergel, E;Jeunemaitre, X
粘液瘤性二尖瓣脱垂（MMVP），也称为巴洛病，是一种常见的心脏异常，影响高达5%的人口。其特征是组织过多，导致二尖瓣瓣叶鼓起，有时并发脱垂。典型的组织学表现包括粘液瘤样变性和胶原蛋白和弹性蛋白的降解。以前的报告提出了一个常染色体显性遗传的特点，年龄和性别依赖性的表达。通过对17例二尖瓣修复术患者的一级亲属进行系统的超声心动图筛查，我们确定了4个显示这种遗传的家系。对信息量最大的系谱（24个个体，三代）的全基因组连锁分析显示，定位到染色体16 p的标记具有显著连锁，D16 S3068具有两点最大LOD得分（在θ = 0时Z（max）= 3.30）。在第二个家族中证实了与D16 S3068的连锁（在θ = 0处Z（max）= 2.02），但排除了其余两个家族，从而证明了该疾病的遗传异质性。多点连锁分析进行，与9个额外的标记，对两个家庭的连锁D16 S3133的最大多点LOD得分为5.45和5.68，根据保守和严格的模型，分别。单倍型分析确定了一个5-cM的最小MMVP-1位点之间的D16 S3068（16p11.2）和D16 S420（16p12.1）和34-cM的最大间隔之间的D16 S404和D16 S3068时，重组事件只考虑在受影响的个人。该位点的鉴定代表了二尖瓣脱垂新分子分类的第一步。
Myxomatous mitral-valve prolapse (MMVP), also called Barlow disease, is a common cardiac abnormality and affects up to 5% of the population. It is characterized by an excess of tissue that leads to billowing of the mitral leaflets, sometimes complicated by prolapse. Typical histological findings include myxomatous degeneration and degradation of collagen and elastin. Previous reports have proposed an autosomal dominant inheritance of the trait, with age- and sex-dependent expression. By systematic echocardiographic screening of the first-degree relatives of 17 patients who underwent mitral-valve repair, we have identified four pedigrees showing such an inheritance. Genomewide linkage analysis of the most informative pedigree (24 individuals, three generations) showed a significant linkage for markers mapping to chromosome 16p, with a two-point maximum LOD score for D16S3068 (Z(max) = 3.30 at theta = 0). Linkage to D16S3068 was confirmed in a second family (Z(max) = 2.02 at theta = 0) but was excluded for the two remaining families, thus demonstrating the genetic heterogeneity of the disease. Multipoint linkage analysis performed, with nine additional markers, on the two families with linkage gave maximum multipoint LOD scores of 5.45 and 5.68 for D16S3133, according to a conservative and a stringent model, respectively. Haplotype analysis defined a 5-cM minimal MMVP-1 locus between D16S3068 (16p11.2) and D16S420 (16p12.1) and a 34-cM maximal interval between D16S404 and D16S3068 when recombination events were taken into account only in affected individuals. The identification of this locus represents a first step toward a new molecular classification of mitral-valve prolapse.