香港华人肥厚性心肌病的遗传格局。

IF 2.8 3区生物学 Q2 GENETICS & HEREDITY

Frontiers in Genetics Pub Date : 2025-05-16 eCollection Date: 2025-01-01 DOI:10.3389/fgene.2025.1583838

Derek P H Lee, Ye Cao, Lilei Zhang

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引用次数: 0

摘要

亚洲人群在肥厚性心肌病（HCM）基因组数据库中的代表性不足，目前主要由高加索人群主导。我们的目的是描述香港华人人群中HCM患者的遗传景观。方法：从2023年3月到2024年3月，在香港的一个三级中心招募了53名临床诊断为HCM的不相关患者，并使用标准化的19个基因面板进行了基因检测。结果：在这项队列研究中，我们确定了13例（24.5%）患者具有显性致病性或可能致病性（P/LP）变异，12例（22.6%）患者具有显性未知意义变异（VUS）。发现的大多数P/LP变异发生在MYBPC3 （46.2%, n = 6）或MYH7 （38.5%, n = 5）。在5例患者中发现了新的遗传变异。在同一患者中发现多个遗传变异是常见的（13.2%,n = 7）。所有致病变异都很罕见，等位基因频率为MYH7:c。1987C>T （p.a g663cys）致病性错义变异（n = 2）， MYBPC3:c。1038_1042dup （p.Met348Thrfs*4）致病性截断变异（n = 3）和MYBPC3:c。1000G>A （p.Glu334Lys）错义VUS （n = 3）。P/LP变异患者发生左心室功能障碍的风险增加（P = 0.012）。结论：本研究揭示了香港华人人群HCM的遗传格局。我们在我们的HCM队列中发现了几种复发变异和新变异。P/LP变异患者发生左心室功能障碍的风险增加。未来对这些复发变异的潜在创始效应、多种变异的累积效应以及HCM患者的纵向随访的研究将是有用的。

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Genetic landscape of hypertrophic cardiomyopathy in Hong Kong Chinese population.

Introduction: 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.

Methods: 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.

Results: 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 MYBPC3 (46.2%, n = 6) or MYH7 (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 MYH7:c.1987C>T (p.Arg663Cys) pathogenic missense variant (n = 2), MYBPC3:c.1038_1042dup (p.Met348Thrfs*4) pathogenic truncating variant (n = 3) and MYBPC3: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).

Conclusion: 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.

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来源期刊

Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

5.50

自引率

8.10%

发文量

3491

审稿时长

14 weeks

期刊介绍： Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.