A Heterozygous Phospholamban Variant(p.R14del)Leads to Left Ventricular Involvement and Heart Failure Phenotypes in Arrhythmogenic Right Ventricular Cardiomyopathy  

作　　者：Han Mo Xiumeng Hua Mengni Bao Zhe Sun Xiao Chen Mengda Xu Jiangping Song 

机构地区：[1]Shenzhen Key Laboratory of Cardiovascular Disease,Fuwai Hospital Chinese Academy of Medical Sciences,Shenzhen 518057,China [2]State Key Laboratory of Cardiovascular Disease,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,167A Beilishi Road,Xi Cheng District,Beijing 100037,China [3]Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials,Animal Experimental Centre,Fuwai Hospital,National Center for Cardiovascular Disease,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China

出　　处：《Phenomics》2024年第1期13-23,共11页表型组学（英文）

基　　金：the National Natural Science Foundation for Distinguished Young Scholars of China(Grant No.82125004);the Shenzhen Science and Technology Innovation Commission(Grant No.JCYJ20220818103414030);the National Natural Science Foundation of China(Grant No.82300397);the key project of Shenzhen Basic Research Program(Natural Science Foundation of Shenzhen,Grant No.20220241);the Program for Guangdong Introducing Innovative and Enterpreneurial Teams(Grant No.2019ZT08Y481).

摘　　要：This study aimed to determine the prevalence and clinical features of Arrhythmogenic Right Ventricular Cardiomyopathy(ARVC)caused by pathogenic mutations in the Phospholamban(PLN)gene.The study included 170 patients who had a confrmed diagnosis of ARVC and underwent PLN genetic screening using next-generation sequencing.The fndings of this study provide valuable insights into the association between PLN mutations and ARVC,which can aid in the development of more efective diagnostic and treatment strategies for ARVC patients.Out of the patients evaluated,six had a rare pathogenic mutation in PLN with the same p.R14del variant.Family screening revealed that heterozygous carriers of p.R14del exhibited a defnite ARVC phenotype.In clinical studies,individuals with the p.R14del mutation experienced a similar rate of malignant arrhythmia events as those with classic desmosome mutations.After adjusting for covariates,individuals with PLN mutations had a two point one seven times greater likelihood of experiencing transplant-related risks compared to those who did not possess PLN mutations(95%CI 1.08–6.82,p=0.035).The accumulation of left ventricular fat and fbers is a pathological marker for ARVC patients with p.R14del mutations.In a cohort of 170 Chinese ARVC patients,three point fve percent of probands had the PLN pathogenic variant(p.R14del)and all were female.Our data shows that PLN-related ARVC patients are at high risk for ventricular arrhythmias and heart failure,which requires clinical diferentiation from classic ARVC.Furthermore,carrying the p.R14del mutation can be an independent prognostic risk factor in ARVC patients.

关 键 词：Arrhythmogenic right ventricular cardiomyopathy PHOSPHOLAMBAN Left ventricular involvement Heart failure Risk stratifcation 

分 类 号：R541.7[医药卫生—心血管疾病] R541.6[医药卫生—内科学]