3例PKP2新致病变异致心律失常性心肌病患者临床特征分析

doi:10.3969/j.issn.1674-8115.2026.07.011

上海交通大学学报（医学版） ›› 2026, Vol. 46 ›› Issue (7): 928-937.doi: 10.3969/j.issn.1674-8115.2026.07.011

• 论著 · 临床研究 • 上一篇

3例PKP2新致病变异致心律失常性心肌病患者临床特征分析

倪璐彦¹^,², 巫辰¹, 陶政宇¹, 王晓柠¹, 张芷萱¹, 董佳炜¹, 姜萌¹()

^1.上海交通大学医学院附属仁济医院心血管内科，上海 200127
^2.上海交通大学医学院附属仁济医院浦南分院心血管内科，上海 200125

收稿日期:2025-09-10 接受日期:2026-02-06 出版日期:2026-07-28 发布日期:2026-07-28
通讯作者: 姜　萌，教授，博士；电子信箱：jiangmeng0919@163.com。
基金资助:
国家自然科学基金(U21A20341);国家自然科学基金(82470394);上海市科学技术委员会项目(25XF3201500);上海市科学技术委员会项目(24DZ2202700);上海市科学技术委员会项目(22DZ2292400);上海市卫生健康委员会项目(202440156);上海市卫生健康委员会项目(2023ZZ02021);上海市卫生健康委员会项目(19DZ2230300);上海申康医院发展中心项目(SHDC2025CCS037);上海交通大学项目(YG2026ZD09);上海交通大学医学院“双百人”项目(20172014);国家卫生健康委能力建设和继续教育中心慢性病管理研究项目(GWJJMB202510021009)

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

Ni Luyan¹^,², Wu Chen¹, Tao Zhengyu¹, Wang Xiaoning¹, Zhang Zhixuan¹, Dong Jiawei¹, Jiang Meng¹()

^1.Department of Cardiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
^2.Department of Cardiology, Punan Branch, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China

Received:2025-09-10 Accepted:2026-02-06 Online:2026-07-28 Published:2026-07-28
Contact: Jiang Meng, E-mail: jiangmeng0919@163.com.
Supported by:
National Natural Science Foundation of China(U21A20341);Project of Shanghai Municipal Science and Technology Commission(25XF3201500);Project of Shanghai Municipal Health Commission(202440156);Program of Shanghai Hospital Development Center(SHDC2025CCS037);Program of Shanghai Jiao Tong University(YG2026ZD09);Project of “Two-hundred Talents” Program of Shanghai Jiao Tong University School of Medicine(20172014);Chronic Disease Management Research Project of National Health Commission Capacity Building and Continuing Education Center(GWJJMB202510021009)

摘要/Abstract

摘要：

目的·报道在中国人群中新发现的PKP2致病基因变异，分析其与致心律失常性心肌病临床表型的关联。方法·收集251例中国不明原因心肌病患者临床资料，包括基因检测结果、影像学特征等。对所有测得的罕见变异进行全外显子测序及Sanger验证，分析携带PKP2变异患者的临床表型。结果·8例诊断为致心律失常性心肌病，其中3例（37.5%）携带国内新发现的PKP2变异。3个变异中，错义变异c.1256T>C（p.Leu419Ser）致左心室受累，错义变异c.2264T>C（p.Leu755Ser）致右心室受累，剪接变异c.2167+1G>C致双心室受累且患者易发室性心动过速。3例患者均伴心律失常，平均发病年龄（23.3±10.5）岁。结论·国内新发现的PKP2致病性变异拓宽了PKP2变异谱，揭示了PKP2基因功能获得性（错义变异）与功能丧失性（剪接变异）突变在导致心室受累模式（单室或双室）及室性心动过速易感性上的关键差异。

关键词: PKP2, 致心律失常性心肌病, 基因型, 临床表型

Abstract:

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 of the PKP2 gene.

Key words: PKP2, arrhythmogenic cardiomyopathy (ACM), genotype, clinical phenotype

中图分类号:

R542.2

倪璐彦, 巫辰, 陶政宇, 王晓柠, 张芷萱, 董佳炜, 姜萌. 3例PKP2新致病变异致心律失常性心肌病患者临床特征分析[J]. 上海交通大学学报（医学版）, 2026, 46(7): 928-937.

Ni Luyan, Wu Chen, Tao Zhengyu, Wang Xiaoning, Zhang Zhixuan, Dong Jiawei, Jiang Meng. Analysis of clinical characteristics of three patients with arrhythmogenic cardiomyopathy carrying novel pathogenic PKP2 variants[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(7): 928-937.

图/表 10

图1 病例1的Sanger测序结果（A）及家系图（B）

Fig 1 Sanger sequencing results (A) and pedigree chart (B) of Case 1

图2 病例2的Sanger测序结果（A）及家系图（B）

Fig 2 Sanger sequencing results (A) and pedigree chart (B) of Case 2

图3 病例3的Sanger测序结果（A）及家系图（B）

Fig 3 Sanger sequencing results (A) and pedigree chart (B) of Case 3

图4 错义变异物种保守性分析

Fig 4 Species conservation analysis of missense variants

图5 基因 PKP2 野生型（A）及p.Leu419Ser变异后(B)的氨基酸疏水性Note： The gradient from red to white represents decreasing hydrophobicity.

Fig 5 Hydrophobicity of amino acids in the wild-type (A) and p.Leu419Ser-variation (B) PKP2 gene

图6 基因 PKP2 野生型(A)及p.Leu419Ser变异后(B)的静电势能Note： The predicted electrostatic potentials of the wild-type and mutant of the PKP2 gene were mapped onto the surface, and colored with a gradient from red (negative) to blue (positive).

Fig 6 Electrostatic potentials of the wild-type (A) and p.Leu419Ser-variation (B) PKP2 gene

图7 野生型(A)及p.Leu419变异后(B)的 PKP2 基因第419位氨基酸氢键

Fig 7 Hydrogen bonds of amino acid at position 419 in the wild-type (A) and p.Leu419Ser-variation (B) PKP2 gene

图8 病例1心电图(A)、UCG(B、C)及CMR(D⁓G)表现Note： A. T-wave inversion (arrows) in leads Ⅱ, aVF and V1, and atrial premature beats (frame). B. Enlarged left heart, reduced global left ventricular myocardial contractility (reduced left ventricular systolic function, LVEF 44%). C. Incoordinate wall motion, reduced amplitude of septal motion (arrows). D. Slightly increased LVEDD (arrow) on cine short-axis sequence. E. Slightly increased LVESD (arrow) on cine short-axis sequence. F. T2 fat-saturated imaging shows no myocardial edema. G. LGE imaging shows no myocardial fibrosis or injury.

Fig 8 Electrocardiogram(A), UCG (B/C), and CMR(D-G) findings in Case 1

图9 病例2心电图(A)及CMR(B⁓E)表现Note： A. Low voltage (circle) in all leads, complete right bundle branch block (frame), first-degree atrioventricular block (bule arrow), flattened and inverted T waves (red arrow) in leads Ⅱ, Ⅲ, aVF, and V1-V6. B. Cine short-axis sequence shows enlargement of both left and right ventricular internal diameters at end-diastole, small aneurysm-like changes in the right ventricular free wall, and abundant fat (arrow) in the right ventricle. C. Cine short-axis sequence shows enlargement of both left and right ventricular internal diameters at end-systole, reduced systolic function of both ventricles, small aneurysm-like changes (arrow) in the right ventricular free wall, and abundant fat in the right ventricle. D. T2 fat suppression shows edema (arrow) in the right ventricular free wall (+), with pericardial fat suppressed and darkened. E. LGE imaging shows delayed enhancement (arrow) in the right ventricular free wall (+).

Fig 9 Electrocardiogram (A) and CMR (B-E) findings in Case 2

图10 病例3 UCG（A）、心电图(B、C)及CMR(D⁓G)表现Note： A. No significant abnormalities found on echocardiography. B. Paroxysmal ventricular tachycardia frame in Holter electrocardiogram. C. Sinus tachycardia and frequent premature ventricular contractions in resting electrocardiogram (arrows). D. Cine short-axis sequence shows increased left ventricular cavity diameter at end-diastole, symmetrically mild thickening of the left ventricular wall, and reduced diastolic function of both left and right ventricles (arrows). E. Cine short-axis sequence shows increased left ventricular cavity diameter at end-systole, symmetrically mild thickening of the left ventricular wall, and reduced systolic function of both left and right ventricles (arrows). F. T2 fat suppression shows no myocardial edema. G. LGE imaging shows linear delayed enhancement (arrows) in the basal septum and lateral wall.

Fig 10 UCG (A), electrocardiogram (B/C), and CMR (D-G) findings in Case 3

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3例PKP2新致病变异致心律失常性心肌病患者临床特征分析

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

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