■关于肥厚型心肌病(HCM)患者亲属的疾病表达的证据很少。这些信息对家庭筛查计划具有重要意义,遗传咨询,和受影响家庭的管理。
■这项研究的目的是调查在公认的HCM基因中携带致病性/可能致病性(P/LP)变异的索引患者亲属的疾病表达和外显率。
■共有453名连续且无关的HCM指数患者接受了临床和遗传学调查。共有903名基因型阳性指数患者的亲属被邀请进行临床调查和基因检测。恍惚,疾病表达,在携带P/LP变异的个体中调查了主要不良心脏事件(MACE)的发生率.
■40%(183/453)的索引患者携带P/LP变异。有P/LP变异的指数患者的所有亲属中有百分之八十四(757/903)可用于调查,其中54%(407/757)携带P/LP变体。亲属中HCM的外显率为39%(160/407)。患有HCM和指数患者的亲属在相似的年龄(43±18岁vs46±15岁;P=0.11)。在8年的随访中,MACE的临床特征和发生率没有差异。
■在识别的疾病基因中携带P/LP变异的索引患者和受影响亲属中HCM的疾病表达相似,经历MACE的风险相等。这些发现为支持基因型阳性HCM家庭的家庭筛查和随访提供了证据,以改善管理并减少亲属中不良疾病并发症的数量。
UNASSIGNED: Little evidence is available on the disease expression in relatives of index patients with hypertrophic cardiomyopathy (HCM). This information has important implications for family screening programs, genetic counseling, and management of affected families.
UNASSIGNED: The purpose of this study was to investigate the disease expression and penetrance in relatives of index patients carrying pathogenic/likely pathogenic (P/LP) variants in recognized HCM genes.
UNASSIGNED: A total of 453 consecutive and unrelated HCM index patients underwent clinical and genetic investigations. A total of 903 relatives of genotype-positive index patients were invited for clinical investigations and genetic testing. Penetrance, disease expression, and incidence rates of major adverse cardiac events (MACEs) were investigated in individuals carrying P/LP variants.
UNASSIGNED: Forty percent (183/453) of index patients carried a P/LP variant. Eighty-four percent (757/903) of all relatives of index patients with P/LP variants were available for the investigation, of whom 54% (407/757) carried a P/LP variant. The penetrance of HCM among relatives was 39% (160/407). Relatives with HCM and index patients were diagnosed at a similar age (43 ± 18 years vs 46 ± 15 years; P = 0.11). There were no differences in clinical characteristics or incidence rates of MACE during 8 years of follow-up.
UNASSIGNED: The disease expression of HCM among index patients and affected relatives carrying P/LP variants in recognized disease genes was similar, with an equal risk of experiencing MACE. These findings provide evidence to support family screening and follow-up of genotype-positive HCM families to improve management and diminish the number of adverse disease complications among relatives.