Autosomal Recessive Catecholamine- or Exercise-Induced Polymorphic Ventricular Tachycardia: Clinical Features and Assignment of the Disease Gene to Chromosome 1p13-21
Autosomal Recessive Catecholamine- or Exercise-Induced Polymorphic Ventricular Tachycardia: Clinical Features and Assignment of the Disease Gene to Chromosome 1p13-21
复制标题
DOI：
10.1161/01.cir.103.23.2822
复制
发表时间：
2001-06
期刊：
影响因子：
--
通讯作者：
H. Lahat;M. Eldar;E. Levy-Nissenbaum;T. Bahan;E. Friedman;A. Khoury;A. Lorber;D. Kastner;B. Goldman;E. Pras
中科院分区：
文献类型：
--
作者：
H. Lahat;M. Eldar;E. Levy-Nissenbaum;T. Bahan;E. Friedman;A. Khoury;A. Lorber;D. Kastner;B. Goldman;E. Pras
背景- 2个常染色体显性遗传家系的致病基因定位于染色体1 q42 -43。本研究的目的是描述以色列贝都因部落中该疾病的临床特征，并绘制疾病基因图谱。方法和结果-在这个贝都因部落中，来自7个相关家庭的9名儿童（年龄，7±4岁）在过去10年中突然死亡，另外12名儿童从6±3岁开始患有复发性晕厥和癫痫发作。受影响个体的父母无症状，并且都是相关的（第一，第二或第三代堂兄弟）。分离分析提示为常染色体隐性遗传。发现所有12例有症状的患者和1例无症状的同胞（平均年龄，13±7岁）有相对静息心动过缓（64±13 bpm，而未受影响的同胞为93±12 bpm），以及由跑步机或异丙肾上腺素输注诱导的PVT，平均窦性心率为110±10 bpm。患者对β-受体阻滞剂治疗反应良好。使用多态性DNA标记的全基因组搜索将疾病位点定位到染色体1 p13 -21上的16兆碱基间隔。在D1 S189 =0.00时获得的最大lod评分为8.24。对编码ItO钾通道转运蛋白的基因KCND 3进行测序，未发现任何显著的序列改变。结论：这种独特的常染色体隐性遗传性PVT影响幼儿，如果不治疗可能致命。连锁分析将这种疾病映射到染色体1 p13 -21。
Background—Catecholaminergic polymorphic ventricular tachycardia (PVT) is characterized by episodes of syncope, seizures, or sudden death in response to physiological or emotional stress. In 2 families with autosomal dominant inheritance, the disease gene was mapped to chromosome 1q42-43. The objectives of this study were to characterize the clinical features of the disease in a Bedouin tribe from Israel and to map the disease gene. Methods and Results—In this Bedouin tribe, 9 children (age, 7±4 years) from 7 related families have died suddenly during the past decade, and 12 other children suffered from recurrent syncope and seizures starting at the age of 6±3 years. Parents of affected individuals were asymptomatic and were all related (first-, second-, or third-degree cousins). Segregation analysis suggested autosomal recessive inheritance. All 12 symptomatic patients and 1 asymptomatic sibling (mean age, 13±7 years) were found to have a relative resting bradycardia (64±13 bpm, versus 93±12 bpm in the unaffected siblings), as well as PVT induced by treadmill or isoproterenol infusion and appearing at a mean sinus rate of 110±10 bpm. Patients responded favorably to treatment with -blockers. A genome-wide search using polymorphic DNA markers mapped the disease locus to a 16-megabase interval on chromosome 1p13-21. A maximal lod score of 8.24 was obtained with D1S189 at =0.00. Sequencing of KCND3, a gene that encodes an ItO potassium channel transporter, did not reveal any significant sequence alterations. Conclusions—This unique form of autosomal recessive PVT affects young children and may be lethal if left untreated. Linkage analysis maps this disorder to chromosome 1p13-21.