Lee Derek P H, Cao Ye, Zhang Lilei
Department of Medicine, Queen Elizabeth Hospital, Kowloon, Hong Kong SAR, China.
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Front Genet. 2025 May 16;16:1583838. doi: 10.3389/fgene.2025.1583838. eCollection 2025.
Asian populations are underrepresented in the hypertrophic cardiomyopathy (HCM) genomic databases, which are currently largely dominated by Caucasian population. We aim to characterize the genetic landscape of HCM in patients from Hong Kong Chinese population.
From March 2023 to March 2024, fifty-three unrelated patients with an unequivocal clinical diagnosis of HCM were enrolled at a single tertiary center in Hong Kong and underwent genetic testing using a standardized 19-gene panel.
In this cohort study, we identified 13 patients (24.5%) with a predominant pathogenic or likely pathogenic (P/LP) variant and 12 patients (22.6%) with a predominant variant of unknown significance (VUS). Most of the P/LP variants identified were in (46.2%, n = 6) or (38.5%, n = 5). Novel genetic variants were identified in 5 patients. Multiple genetic variants identified in the same patient were common (13.2%, n = 7). All disease-causing variants are rare with allele frequencies <0.00005 in all populations and <0.0002 in East Asian subpopulation. Specifically in this unrelated cohort, we identified several recurrent variants including :c.1987C>T (p.Arg663Cys) pathogenic missense variant (n = 2), :c.1038_1042dup (p.Met348Thrfs*4) pathogenic truncating variant (n = 3) and :c.1000G>A (p.Glu334Lys) missense VUS (n = 3). Patients with P/LP variants were associated with an increased risk of developing left ventricular dysfunction (p = 0.012).
Our study provided insight into the genetic landscape of HCM in Hong Kong Chinese population. We identified several recurrent variants and novel variants in our HCM cohort. Patients with P/LP variants were associated with an increased risk of developing left ventricular dysfunction. Future studies on the potential founder effects of these recurrent variants, cumulative effects of multiple variants, and longitudinal follow up of HCM patients would be useful.
肥厚型心肌病（HCM）基因组数据库中亚洲人群的代表性不足，目前这些数据库主要由白种人主导。我们旨在描绘香港中国人群中HCM患者的遗传图谱。
2023年3月至2024年3月，在香港的一家三级中心招募了53例临床诊断明确的非亲缘关系HCM患者，并使用标准化的19基因检测板进行基因检测。
在这项队列研究中，我们鉴定出13例（24.5%）具有主要致病或可能致病（P/LP）变异的患者和12例（22.6%）具有主要意义未明变异（VUS）的患者。鉴定出的大多数P/LP变异位于（46.2%，n = 6）或（38.5%，n = 5）。在5例患者中鉴定出了新的基因变异。同一患者中鉴定出多个基因变异很常见（13.2%，n = 7）。所有致病变异在所有人群中的等位基因频率均<0.00005，在东亚亚人群中<0.0002。具体在这个非亲缘队列中，我们鉴定出了几种反复出现的变异，包括：c.1987C>T（p.Arg663Cys）致病错义变异（n = 2）、：c.1038_1042dup（p.Met348Thrfs*4）致病截短变异（n = 3）和：c.1000G>A（p.Glu334Lys）错义VUS（n = 3）。具有P/LP变异的患者发生左心室功能障碍的风险增加（p = 0.012）。
我们的研究为香港中国人群中HCM的遗传图谱提供了见解。我们在HCM队列中鉴定出了几种反复出现的变异和新变异。具有P/LP变异的患者发生左心室功能障碍的风险增加。未来对这些反复出现变异的潜在奠基者效应、多个变异的累积效应以及HCM患者的纵向随访研究将是有用的。
