Localization of a gene responsible for arrhythmogenic right ventricular dysplasia to chromosome 3p23
Localization of a gene responsible for arrhythmogenic right ventricular dysplasia to chromosome 3p23
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DOI：
10.1161/01.cir.98.25.2791
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发表时间：
1998-12-22
期刊：
影响因子：
37.8
通讯作者：
Roberts, R
中科院分区：
文献类型：
--
作者：
Ahmad, F;Li, DX;Roberts, R
致心律失常性右心室发育不良（ARVD）是一种家族性心肌病，发病率为1/5000，其特征是肌细胞被脂肪和纤维组织替代。临床表现包括右心室的结构和功能异常以及心律失常，导致每年2.5%的猝死率。四个位点已被映射，但没有基因已被确定为yest.Methods和结果，我们确定了一个大家庭的成员超过200 ARVD分离作为一个常染色体显性性状影响10个生活的个人。ARVD的诊断基于国际诊断标准，包括病史、体格检查、EGG、超声心动图、右心室血管造影、肌内膜活检和24小时动态EGG。从149名家庭成员中收集了血液DNA。对257个多态性微卫星标记进行遗传连锁分析，排除了先前已知的ARVD基因座，并在3 p23处发现了一个新的基因座。另外20个标记物的分析进一步定义了该区域。用标记D3 S3613在θ =0%重组时获得6.91的优势分数的峰值对数。单倍型分析确定了标记D3 S3610和D3 S3659之间的9.3 cM. Conclusions之间的共享区域一个新的基因座ARVD已被定位到3 p23和该区域缩小到9.3 cM。该基因的鉴定将允许遗传筛查和特异性诊断具有多变非特异性发现的疾病。它也应该提供基本的洞察力，了解心脏腔室特异性基因表达和/或心肌细胞凋亡的机制，在这种疾病中观察到。
Background-Arrhythmogenic right ventricular dysplasia (ARVD), a familial cardiomyopathy occurring with a prevalence of 1 in 5000, is characterized by replacement of myocytes with fatty and fibrous tissue. Clinical manifestations include structural and functional abnormalities of the right ventricle and arrhythmias, leading to a sudden death rate of 2.5% per year. Four loci have been mapped, but no gene has been identified as yet.Methods and Results-We identified a large family of >200 members with ARVD segregating as an autosomal dominant trait affecting 10 living individuals. The diagnosis of ARVD was based on international diagnostic criteria including history, physical examination, EGG, echocardiogram, right ventricular angiogram, endomyocardial biopsy, and 24-hour ambulatory EGG. Blood was collected for DNA from 149 family members. Analysis of 257 polymorphic microsatellite markers by genetic linkage excluded previously known loci for ARVD and identified a novel locus at 3p23. Analysis of an additional 20 markers further defined the region. A peak logarithm of the odds score of 6.91 was obtained with marker D3S3613 at theta=0% recombination. Haplotype analysis identified a shared region between markers D3S3610 and D3S3659 of 9.3 cM.Conclusions-A novel locus for ARVD has been mapped to 3p23 and the region narrowed to 9.3 cM. Identification of the gene will allow genetic screening and a specific diagnosis for a disease with protean nonspecific findings. It should also provide insight fundamental to understanding cardiac chamber-specific gene expression and/or the mechanism of myocyte apoptosis observed in this disease.