Analysis of clinical characteristics of three patients with arrhythmogenic cardiomyopathy carrying novel pathogenic PKP2 variants

作者：Ni Luyan, Chen Wu, Tao Zhengyu, Wang Xiaoning, Zhang Zhixuan, Dong Jiawei, Jiang Meng · 发表于：DOAJ (DOAJ: Directory of Open Access Journals) · 年份：2026 · DOI：10.3969/j.issn.1674-8115.2026.07.011 · 研究领域：Cardiovascular Effects of Exercise、Cardiomyopathy and Myosin Studies、Cardiac electrophysiology and arrhythmias

Objective·To report newly discovered pathogenic variants of the PKP2 gene in the Chinese population and analyze their association with the clinical phenotype of arrhythmogenic cardiomyopathy (ACM).Methods·Clinical data, including genetic test results and imaging features, were collected from 251 Chinese patients with unexplained cardiomyopathy. All detected rare variants were analyzed by whole-exome sequencing and confirmed by Sanger sequencing. The clinical phenotypes of patients carrying PKP2 variants were analyzed.Results·Eight patients were diagnosed with arrhythmogenic cardiomyopathy, among whom 3 (37.5%) carried novel PKP2 variants in the Chinese population. Among the three variants, the missense variant c.1256T>C (p.Leu419Ser) was associated with left ventricular involvement, the missense variant c.2264T>C (p.Leu755Ser) was associated with right ventricular involvement, and the splice-site variant c.2167+1G>C was associated with biventricular involvement and increased susceptibility to ventricular tachycardia. All three patients presented with arrhythmias, and the mean age at disease onset was (23.3±10.5) years.Conclusion·The novel pathogenic PKP2 variants identified in Chinese population expand the variant spectrum of the PKP2 gene. Key differences in ventricular involvement patterns (univentricular or biventricular) and susceptibility to ventricular tachycardia are revealed between gain-of-function (missense variants) and loss-of-function (splicing variant) mutations...