Faculty of Medicine Ramathibodi Hospital, Department of Medicine, Mahidol University, Bangkok, Thailand.
Faculty of Medicine Ramathibodi Hospital, Center for Medical Genomics, Mahidol University, Bangkok, Thailand.
PLoS One. 2022 Sep 27;17(9):e0267770. doi: 10.1371/journal.pone.0267770. eCollection 2022.
Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are the most common referrals in the Inherited Cardiovascular Condition (ICC) Genetics Service. Several issues must be discussed with patients and their families during the genetic consultation session, including the options for genetic testing and cardiovascular surveillance in family members. We developed an ICC registry and performed next-generation-based DNA sequencing for all patients affected by non-syndromic HCM and idiopathic DCM in our joint specialist genetics service. The target gene sequencing panel relied on the Human Phenotype Ontology with 237 genes for HCM (HP:0001639) and 142 genes for DCM (HP:0001644). All subjects were asked to contact their asymptomatic first-degree relatives for genetic counseling regarding their risks and to initiate cardiovascular surveillance and cascade genetic testing. The study was performed from January 1, 2014, to December 31, 2020, and a total of 62 subjects (31-HCM and 31-DCM) were enrolled. The molecular detection frequency was 48.39% (32.26% pathogenic/likely pathogenic, 16.13% variant of uncertain significance or VUS for HCM, and 25.81% (16.13% pathogenic/likely pathogenic, 9.68% VUS) for DCM. The most prevalent gene associated with HCM was MYBPC3. The others identified in this study included ACTN2, MYL2, MYH7, TNNI3, TPM1, and VCL. Among the DCM subjects, variants were detected in two cases with the TTN nonsense variants, while the others were missense and identified in MYH7, DRSP3, MYBPC3, and SCN5A. Following the echocardiogram surveillance and cascade genetic testing in the asymptomatic first-degree relatives, the detection rate of new cases was 8.82% and 6.25% in relatives of HCM and DCM subjects, respectively. Additionally, a new pre-symptomatic relative belonging to an HCM family was identified, although the genomic finding in the affected case was absent. Thus, ICC service is promising for the national healthcare system, aiming to prevent morbidity and mortality in asymptomatic family members.
肥厚型心肌病 (HCM) 和扩张型心肌病 (DCM) 是遗传性心血管疾病 (ICC) 遗传服务中最常见的转诊疾病。在遗传咨询会议期间，必须与患者及其家属讨论几个问题，包括对家庭成员进行基因检测和心血管监测的选择。我们在联合专科遗传服务中为所有非综合征性 HCM 和特发性 DCM 患者开发了一个 ICC 登记处，并进行了基于下一代的 DNA 测序。目标基因测序面板基于人类表型本体论，包含 237 个 HCM 基因（HP：0001639）和 142 个 DCM 基因（HP：0001644）。所有患者均被要求联系无症状一级亲属进行遗传咨询，了解其风险，并启动心血管监测和级联基因检测。该研究于 2014 年 1 月 1 日至 2020 年 12 月 31 日进行，共纳入 62 名患者（31 名 HCM 和 31 名 DCM）。分子检测频率为 48.39%（32.26%为致病性/可能致病性，16.13%为 HCM 的意义不明或不确定的变异，25.81%（16.13%为致病性/可能致病性，9.68%为意义不明或不确定的变异）为 DCM。与 HCM 相关的最常见基因是 MYBPC3。本研究还鉴定出 ACTN2、MYL2、MYH7、TNNI3、TPM1 和 VCL。在 DCM 患者中，在 2 例 TTN 无义变异患者中检测到变异，而其他患者则为错义变异，发生在 MYH7、DRSP3、MYBPC3 和 SCN5A 中。在对无症状一级亲属进行超声心动图监测和级联基因检测后，HCM 和 DCM 患者的亲属中新病例的检出率分别为 8.82%和 6.25%。此外，还发现了一个属于 HCM 家族的新的无症状亲属，但受累病例的基因组发现缺失。因此，ICC 服务有望为国家医疗保健系统服务，旨在预防无症状家庭成员的发病率和死亡率。
