Wang Y, Wang B, Zhao X L, Liu J, Yuan J R, Zhao J, Zhang L L, Liang C T, Wang J, Liu L W
Department of Ultrasound, the First Affiliated Hospital of Air Force Medical University (Xijing Hospital), Hypertrophic Cardiomyopathy International Cooperation Center, the First Affiliated Hospital of Air Force Medical University (Xijing Hospital), Multidisciplinary Consultation Center of Hypertrophic Cardiomyopathy, Shaanxi Province, Multidisciplinary Clinic and Genetic Counseling Center of Hypertrophic Cardiomyopathy, Xijing Hospital, Xi'an710032, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2024 Dec 24;52(12):1383-1389. doi: 10.3760/cma.j.cn112148-20240821-00469.
To analyze the relationship between genotype and clinical phenotype of the MYH7-R453C mutation in five Chinese hypertrophic cardiomyopathy (HCM) families. A retrospective cohort study was conducted on 527 unrelated HCM probands who were first diagnosed at the First Affiliated Hospital of Air Force Medical University (Xijing Hospital) from February 2014 to July 2018, and the high-throughput whole exome targeted sequencing of 96 genes related to hereditary cardiovascular disease was performed on the probands. The probands carrying the MYH7-R453C mutation were screened out, and their family members carrying the mutation were verified using Sanger sequencing. Healthy individuals without family history of genetic diseases from the same period and ethnicity were recruited as controls. Clinical data such as echocardiography, 12-lead electrocardiogram, and cardiac magnetic resonance imaging of the probands and their family members were collected, and the correlation between patient genotype and clinical phenotype was analyzed. Endpoint or key events were recorded through hospital re-examination or telephone follow-up. The MYH7-R453C mutation was detected in 5 HCM probands, and clinical data and genetic results of 20 family members, including probands, were collected. Among them, 13 carried the MYH7-R453C mutation, of which 12 were diagnosed with HCM, and one child (F1Ⅲ) experienced early changes of HCM. The seven family members who did not carry the MYH7-R453C mutation had normal echocardiograms and 12-lead electrocardiograms. Among the 12 patients diagnosed with HCM, 2 experienced (F2Ⅱ, F5Ⅰ) sudden cardiac death, 2 experienced (F1Ⅲ, F3Ⅲ) events of sudden cardiac death survival, 2(F1Ⅱ, F3Ⅱ) died from heart failure during the follow-up period. Combined with the initial visit and follow-up, 4 families (F1, F2, F3, F5) had a family history of sudden death, among which 3 families probands or multiple family members experiencing sudden death before the age of 30 and adverse outcomes such as implantation of implantable cardioverter-defibrillators after sudden death survival. In the five families with HCM carrying MYH7-R453C mutations, genotype is highly correlated with clinical phenotype, and patients have a high risk of sudden death and poor prognosis. Early diagnosis of individuals carrying the MYH7-R453C gene mutation, both within the patient's family and in the patients themselves, is crucial for initiating early treatment, preventing sudden death, and assessing prognosis.
分析5个中国肥厚型心肌病（HCM）家系中MYH7-R453C突变的基因型与临床表型之间的关系。对2014年2月至2018年7月在空军军医大学第一附属医院（西京医院）首次确诊的527例无亲缘关系的HCM先证者进行回顾性队列研究，对先证者进行96个遗传性心血管疾病相关基因的高通量全外显子靶向测序。筛选出携带MYH7-R453C突变的先证者，并采用Sanger测序法对其携带该突变的家庭成员进行验证。招募同期同种族无遗传疾病家族史的健康个体作为对照。收集先证者及其家庭成员的超声心动图、12导联心电图和心脏磁共振成像等临床资料，分析患者基因型与临床表型之间的相关性。通过医院复诊或电话随访记录终点事件或关键事件。在5例HCM先证者中检测到MYH7-R453C突变，收集了包括先证者在内的20名家庭成员的临床资料和基因检测结果。其中，13人携带MYH7-R453C突变，其中12人被诊断为HCM，1名儿童（F1Ⅲ）出现HCM早期改变。7名未携带MYH7-R453C突变的家庭成员超声心动图和12导联心电图正常。在12例诊断为HCM的患者中，2例（F2Ⅱ，F5Ⅰ）发生心源性猝死，2例（F1Ⅲ，F3Ⅲ）发生心源性猝死存活事件，2例（F1Ⅱ，F3Ⅱ）在随访期间死于心力衰竭。结合初诊和随访情况，4个家系（F1、F2、F3、F5）有猝死家族史，其中3个家系先证者或多名家庭成员在30岁前发生猝死，猝死存活后出现植入式心律转复除颤器植入等不良后果。在携带MYH7-R453C突变的5个HCM家系中，基因型与临床表型高度相关，患者猝死风险高，预后差。对携带MYH7-R453C基因突变的个体，无论是在患者家族内部还是患者本人，早期诊断对于启动早期治疗、预防猝死和评估预后至关重要。
