Abstract
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.
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Acknowledgments
This study was supported by the Ministry of Science and Technology of China (grant number 2007DFC30340 and 2009DFB30050) and by the National Natural Science Foundation of China (grant number 30971233). We thank the patients for participating in the study. We are grateful to Ferhaan Ahmad for critical reading and helpful ideas of the manuscript.
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Yubao Zou, Jizheng Wang, Xuan Liu, Lei Song and Rutai Hui contributed equally to the study
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Zou, Y., Wang, J., Liu, X. et al. Multiple gene mutations, not the type of mutation, are the modifier of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy. Mol Biol Rep 40, 3969–3976 (2013). https://doi.org/10.1007/s11033-012-2474-2
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DOI: https://doi.org/10.1007/s11033-012-2474-2