基因组连锁扫描确定5p13染色体异常遗传基因位点可阐明新生儿房颤与猝死和多种心肌病有关

作     者：Oberti C. 杜媛 

出 版 物：《世界核心医学期刊文摘（心脏病学分册）》 (Digest of the World Core Medical Journals(Cardiology))

年 卷 期：2005年第1卷第6期

页      面：44-45页

学科分类：1002[医学-临床医学] 100202[医学-儿科学] 10[医学] 

主　　题：染色体异常 心肌病 基因位点 缺血性脑卒中 连锁分析 快速心律失常 常染色体隐性 心房纤颤 携带者 病理生理学 

摘      要：Background-Atrial fibrillation(AF)is the most common sustained cardiac arrhythmia, and patients with AF have a significantly increased risk for ischemic stroke. Approximately 15%of all strokes are caused by AF. The molecular basis and underlying mechanisms and pathophysiology of AF remain largely unknown. Methods and Results-We have identified a large AF family with an autosomal recessive inheritance pattern. The AF in the family manifests with early onset at the fetal stage and is associated with neonatal sudden death and, in some cases, ventricular tachyarrhythmias and waxing and waning cardiomyopathy. Genome-wide linkage analysis was performed for 36 family members and generated a 2-point logarithm of the odds(LOD)score of 3.05 for marker D5S455. The maximum multipoint LOD score of 4.10 was obtained for 4 markers: D5S426, D5S493, D5S455, and D5S1998. Heterozygous carriers have significant prolongation of P-wave duration on ECGs compared with noncarriers(107 versus 85 ms on average; P=0.000012), but no differences between these 2 groups were detected for the PR interval, QRS complex, ST-segment duration, T-wave duration, QTc, and R-R interval(P 0.05). Conclusions-Our findings demonstrate that AF can be inherited as an autosomal recessive trait and define a novel genetic locus for AF on chromosome 5p13(arAF1). A genetic link between AF and prolonged P-wave duration was identified. This study provides a framework for the ultimate cloning of the arAF1 gene, which will increase the understanding of the fundamental molecular mechanisms of atrial fibrillation.