Case Report: Identification of novel CDH2 mutation (p. P183A het)-induced arrhythmogenic cardiomyopathy in China
Kun Li1, Yifei Wang1, Jing Yang1
1Department of Cardiology, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.
Insights
This study reports a novel CDH2 gene mutation in a 10-year-old Chinese patient with arrhythmogenic cardiomyopathy. This finding reveals a new mechanism for arrhythmogenic cardiomyopathy involving cell-cell adhesion disruption.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Pediatric Cardiology
Background:
- Arrhythmogenic cardiomyopathy (ACM) is an inherited heart condition characterized by fibrofatty replacement of the heart muscle.
- Genetic variations are a primary cause of ACM, increasing the risk of arrhythmias and sudden cardiac death.
Observation:
- A 10-year-old patient presented with palpitations, premature ventricular contractions, and an epsilon wave on ECG.
- Echocardiography revealed right ventricular enlargement, leading to a clear ACM diagnosis.
- Genetic analysis identified a novel heterozygous missense mutation in the CDH2 gene (c.547C>G, p.P183A).
Findings:
- This is the first reported case of CDH2 mutation-related ACM in the Chinese population.
- The identified mutation (p.P183A) potentially disrupts adherens junctions in intercalated discs.
- This represents a novel mechanism for ACM, distinct from previously described desmosome-related mutations.
Implications:
- The findings expand the understanding of genetic underpinnings of arrhythmogenic cardiomyopathy.
- CDH2 mutations affecting cell-cell adhesion offer a new therapeutic target for ACM.
- This case highlights the importance of genetic testing in pediatric patients with unexplained arrhythmias.
Background:
Arrhythmogenic cardiomyopathy/dysplasia (ACM) is an inheritable heart disease closely related to gene variations induced heart fibrofatty replacement, which increases the risk of arrhythmia events and even sudden cardiac death. In this study, we reported a 10-year-old patient with a novel mutation diagnosed with ACM.
Case Presentation:
We present the case of a 10-year-old patient admitted with recurrent palpitation, whose electrocardiogram suggested the existence of right ventricle origin premature ventricular contractions and ε wave. Furthermore, echocardiography showed an enlarged right ventricle corrected to a body surface area of 29.57 mm/m2. The diagnosis of ACM was clear. Further gene sequencing revealed a novel heterozygous missense mutation of CDH2 (cadherin-2) c.547C > G (p. P183A) that potentially increases ACM risk by affecting adherens junctions of the intercalated discs.
Conclusions:
This is the first case of CDH2 mutation (c.547C > G, p. P183A) related ACM in the Chinese population. Compared to previously reported mutations inducing ACM by affecting desmosome function, the newly reported CDH2 variation revealed a novel potential mechanism that induces ACM by disturbing cell-cell adhesion.
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