Arad Michael, Monserrat Lorenzo, Haron-Khun Shiraz, Seidman Jonathan G, Seidman Christine E, Arbustini Eloisa, Glikson Michael, Freimark Dov
Sheba Medical Center, Tel Hashomer, Israel.
Isr Med Assoc J. 2014 Nov;16(11):707-13.
Hypertrophic cardiomyopathy (HCM) is a familial disease with autosomal dominant inheritance and age-dependent penetrance, caused primarily by mutations of sarcomere genes. Because the clinical variability of HCM is related to its genetic heterogeneity, genetic studies may improve the diagnosis and prognostic evaluation in HCM.
To analyze the impact of genetic diagnosis on the clinical management of HCM.
Genetic studies were performed for either research or clinical reasons. Once the disease-causing mutation was identified, the management plan was reevaluated. Family members were invited to receive genetic counseling and encouraged to be tested for the mutation.
Ten mutations in sarcomere protein genes were identified in 9 probands: 2 novel and 8 previously described. Advanced heart failure or sudden death in a young person prompted the genetic study in 8 of the 9 families. Of 98 relatives available for genotyping, only 53 (54%) agreed to be tested. The compliance was higher in families with sudden death and lower in what appeared to be sporadic HCM or elderly-onset disease. Among the healthy we identified 9 carriers and 19 non-carriers. In 6 individuals the test result resolved an uncertainty about "possible HCM." In several cases the genetic result was also used for family planning and played a role in decisions on cardioverter-defibrillator implantation.
Recurrence of a same mutation in different families created an opportunity to apply the information from the literature for risk stratification of individual patients. We suggest that the clinical context determines the indication for genetic testing and interpretation of the results.
肥厚型心肌病（HCM）是一种常染色体显性遗传且具有年龄依赖性外显率的家族性疾病，主要由肌节基因突变引起。由于HCM的临床变异性与其遗传异质性相关，基因研究可能会改善HCM的诊断和预后评估。
分析基因诊断对HCM临床管理的影响。
出于研究或临床原因进行基因研究。一旦确定致病突变，就重新评估管理计划。邀请家庭成员接受遗传咨询并鼓励他们进行突变检测。
在9名先证者中鉴定出10个肌节蛋白基因突变：2个为新突变，8个为先前已描述的突变。9个家庭中有8个家庭因年轻人出现晚期心力衰竭或猝死而促使进行基因研究。在98名可进行基因分型的亲属中，只有53名（54%）同意接受检测。猝死家庭的依从性较高，而散发性HCM或老年发病疾病家庭的依从性较低。在健康人群中，我们鉴定出9名携带者和19名非携带者。在6名个体中，检测结果解决了关于“可能患有HCM”的不确定性。在一些病例中，基因检测结果还用于计划生育，并在心脏复律除颤器植入决策中发挥作用。
不同家庭中相同突变的复发为应用文献信息对个体患者进行风险分层创造了机会。我们建议临床情况决定基因检测的指征和结果的解释。
