Multiple gene mutations, not the type of mutation, are the modifier of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy
Multiple gene mutations, not the type of mutation, are the modifier of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy
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DOI：
10.1007/s11033-012-2474-2
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发表时间：
2013-06-01
影响因子：
2.8
通讯作者：
Hui, Rutai
中科院分区：
文献类型：
--
作者：
Zou, Yubao;Wang, Jizheng;Hui, Rutai
由于肥厚型心肌病（HCM）的遗传和临床异质性，基因型-表型相关性一直是一个挑战。为了确定中国HCM患者的突变谱，并将基因型与表型相关联，我们使用直接DNA测序法对200名无关的中国成年患者中编码肌节蛋白的8个最常见突变基因进行了系统的突变筛查。在102名突变携带者中共鉴定出98种突变。MYH 7、MYBPC 3、TNNT 2和TNNI 3的突变频率分别为26.0%、18.0%、4.0%和3.5%。在200例基因型HCM患者中，83例携带单一突变，19例（9.5%）携带多种突变。突变数与最大壁厚呈正相关。我们发现特定基因或特定突变与临床表型无关。总之，中国HCM患者的多突变频率高于高加索人群。肌节蛋白的多重突变可能是左室壁厚度的危险因素。
Genotype-phenotype correlation of hypertrophic cardiomyopathy (HCM) has been challenging because of the genetic and clinical heterogeneity. To determine the mutation profile of Chinese patients with HCM and to correlate genotypes with phenotypes, we performed a systematic mutation screening of the eight most commonly mutated genes encoding sarcomere proteins in 200 unrelated Chinese adult patients using direct DNA sequencing. A total of 98 mutations were identified in 102 mutation carriers. The frequency of mutations in MYH7, MYBPC3, TNNT2 and TNNI3 was 26.0, 18.0, 4.0 and 3.5 % respectively. Among the 200 genotyped HCM patients, 83 harbored a single mutation, and 19 (9.5 %) harbored multiple mutations. The number of mutations was positively correlated with the maximum wall thickness. We found that neither particular gene nor specific mutation was correlated to clinical phenotype. In summary, the frequency of multiple mutations was greater in Chinese HCM patients than in the Caucasian population. Multiple mutations in sarcomere protein may be a risk factor for left ventricular wall thickness.