Screening of pathogenic genes in Chinese patients with arrhythmogenic right ventricular cardiomyopathy.
BACKGROUND
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiac disease predominantly caused by mutations in desmosomal protein genes. Previous genetic analyses of the Chinese ARVC population are limited to small size and restriction to a single gene. This study was aimed to investigate the genotype in a large series of Chinese patients with ARVC through comprehensively screening nine ARVC-causing genes.


METHODS
A total of 100 unrelated ARVC patients and 300 age, gender and ethnicity matched healthy controls were genetically tested with multiplexing targeted resequencing for nine previously reported ARVC-causing genes, including plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2, plakoglobin, transforming growth factor beta-3, transmembrane protein 43, desmin and Lamin A/C.


RESULTS
Fifty-nine mutations were identified in 64% of the patients, among which, 93% were located in desmosomal protein genes. Plakophilin-2 mutations accounted for 54% of the total and 58% of the desmosomal mutations, with a truncating mutation type making up about 2/3 of the plakophilin-2 mutations. Only four mutations were found in non-desmosomal genes; two in transmembrane protein 43 and two in transforming growth factor beta-3. Two of them (one of each gene) appeared as single missense mutations. No mutation was identified in desmin or Lamin A/C. Multiple mutations were found in 23% of the patients, with plakophilin-2 being found in 57% of the multi-mutation carriers.


CONCLUSIONS
Plakophilin-2 was the most common gene mutation that was identified in Chinese ARVC patients. Non-desmosomal genes should be added to desmosomal protein genes when performing molecular genetic screening in patients with suspected ARVC.
Arrhythmia Center and Clinical EP Laboratory, State Key Laboratory of Cardiovascular Diseases, National Center for Cardiovascular Disease, Fuwai Hospital, Peking Union Medical College-Chinese Academy of Medical Sciences, Beijing 100037, China.
Jing-Ru
JR
Bao
Ji-Zheng
JZ
Wang
Yan
Y
Yao
Yi-Lu
YL
Wang
Xiao-Han
XH
Fan
Kai
K
Sun
Shu
S
Zhang
Ru-Tai
RT
Hui
Lei
L
Song
D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics* / Q000378:metabolism*; D044466:Asian People; D003893:Desmin / Q000235:genetics; D051301:Desmoglein 2 / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051191:Plakophilins / Q000235:genetics*; D055815:Young Adult; D051185:gamma Catenin / Q000235:genetics
C495314:DSG2 protein, human; D003893:Desmin; D051301:Desmoglein 2; D051191:Plakophilins; D051185:gamma Catenin