Gene mutations in apical hypertrophic cardiomyopathy
Gene mutations in apical hypertrophic cardiomyopathy
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DOI：
10.1161/circulationaha.105.547448
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发表时间：
2005-11-01
期刊：
影响因子：
37.8
通讯作者：
Seidman, CE
中科院分区：
文献类型：
--
作者：
Arad, M;Penas-Lado, M;Seidman, CE
背景资料：位于心尖部的非梗阻性肥厚是肥厚型心肌病（HCM）的一种罕见的形态学变异，通常通过明显的巨大负T波和良性临床过程进一步区分。HCM与典型的肥厚形态与孤立的心尖肥厚之间的遗传关系是不完全understood.Methods和Results;遗传原因进行了调查，在15个先证者与心尖肥厚的DNA序列分析9肌节蛋白基因和其他3个基因（GLA，PRKAG 2，和LAMP 2）牵连在特发性心脏肥大。在7个样本中发现6个肌节基因突变;没有样本包含GLA、PRKAG 2或LAMP 2突变。临床评价显示4例先证者为家族性心尖肥厚型心肌病，3例先证者发现致病突变。两个家族共有一个心脏肌动蛋白Glu 101 Lys错义突变，两个家族的所有成员与HCM的临床表现（n = 16）有心尖肥大。1例先证者和5例家系成员中有1个轻链错义突变Met 149 Val引起心尖段或心室中段肥厚型心肌病，而6例患者亲属具有典型的肥厚型心肌病形态。没有其他的肌节基因突变，在其余的先证者造成心尖HCM在其他family members.Conclusions：肌节蛋白基因突变，导致心尖肥大，而不是更常见的HCM形态反映遗传病因，背景修饰基因，和/或血流动力学因素之间的相互作用。只有有限数量的肌节基因缺陷（例如心脏肌动蛋白Glu 101 Lys）会持续产生顶端HCM。
Background: Nonobstructive hypertrophy localized to the cardiac apex is an uncommon morphological variant of hypertrophic cardiomyopathy (HCM) that often is further distinguished by distinct giant negative T waves and a benign clinical course. The genetic relationship between HCM with typical hypertrophic morphology versus isolated apical hypertrophy is incompletely understood.Methods and Results; Genetic cause was investigated in 15 probands with apical hypertrophy by DNA sequence analyses of 9 sarcomere protein genes and 3 other genes (GLA, PRKAG2, and LAMP2) implicated in idiopathic cardiac hypertrophy. Six sarcomere gene mutations were found in 7 samples; no samples contained mutations in GLA, PRKAG2, or LAMP2. Clinical evaluations demonstrated familial apical HCM in 4 probands, and in 3 probands disease-causing mutations were identified. Two families shared a cardiac actin Glu101Lys missense mutation; all members of both families with clinical manifestations of HCM (n = 16) had apical hypertrophy. An essential light chain missense mutation Met149Val caused apical or midventricular segment HCM in another proband and 5 family members, but 6 other affected relatives had typical HCM morphologies. No other sarcomere gene mutations identified in the remaining probands caused apical HCM in other family members.Conclusions: Sarcomere protein gene mutations that cause apical hypertrophy rather than more common HCM morphologies reflect interactions among genetic etiology, background modifier genes, and/or hemodynamic factors. Only a limited number of sarcomere gene defects (eg, cardiac actin Glu101Lys) consistently produce apical HCM.