The co-segregation of the MYL2 R58Q mutation in Chinese hypertrophic cardiomyopathy family and its pathological effect on cardiomyopathy disarray
Hypertrophic cardiomyopathy (HCM), a major cause of sudden death in youth, is largely affected by genetic factors. The R58Q mutation in the MYL2 gene was identified in some HCM patients and was considered as a deleterious HCM mutation. However, the passing of R58Q between generations along with HCM symptoms was observed only in small families with only two or three members; thus, whether R58Q is as deleterious as previously claimed remains questionable. Here, we reported a large four-generation Chinese family, and found that R58Q existed in all six members with HCM and two healthy juveniles who had not yet developed HCM yet, and presumably in three deceased members who suffered from sudden death. In addition, we also found that compared with other mutations, R58Q had a more severe effect on the cellular level. Therefore, we confirmed that R58Q could be passed from generation to generation along with HCM symptoms and that it was indeed a deleterious mutation for HCM. However, further study is needed to identify additional factors that may determine the various symptoms shown in different family members within the same family.
KeywordsMYL2 R58Q Hypertrophic cardiomyopathy Segregation Pathologic alteration Disorganization
We sincerely thank Dr. Yuanyuan Fu for the kind proof reading of the manuscript. This work was supported by the Starting Fund for 1000 Youth Talents (no. 2013-RSQ02), the Beijing Science and Technology Program (no. Z161100000516154) and the National Natural Science Foundation of China (no. 81570276).
Compliance with ethical standards
Conflict of interest
Kunlun Yin declares that he has no conflict of interest. Yi Ma declares that she has no conflict of interest. Hao Cui declares that he has no conflict of interest. Yang Sun declares that she has no conflict of interest. Bianmei Han declares that she has no conflict of interest. Xuewen Liu declares that she has no conflict of interest. Kun Zhao declares that she has no conflict of interest. Wenke Li declares that he has no conflict of interest. Jingjin Wang declares that she has no conflict of interest. Hongyue Wang declares that he has no conflict of interest. Shuiyun Wang declares that he has no conflict of interest. Zhou Zhou declares that he has no competing interests.
This study was approved by the ethics committee of the institutional review board at Fuwai Hospital. Informed consent was obtained from all individual participants included in the study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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