Desmosomal protein gene mutations of Yunnan unexplained sudden death cases families by ARVC pathological diagnosis
10.3760/cma.j.cn231583-20190401-00075
- VernacularTitle:云南不明原因猝死ARVC病理诊断病例家庭桥粒蛋白基因突变研究
- Author:
Yuebing WANG
1
;
Lin MA
;
Xue TANG
;
Lin YANG
;
Yanmei XI
;
Mengyao SUN
;
Yi DONG
;
Wenli HUANG
;
Puping LEI
Author Information
1. 云南省地方病防治所卫生应急办公室，大理 671000
- From:
Chinese Journal of Endemiology
2020;39(8):551-556
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To expound the pathogenesis relationship between Yunnan unexplained sudden death (YUSD) and desmosomal protein gene mutations of arrhythmogenic right ventricular cardiomyopathy (ARVC).Methods:Four YUSD cases families by ARVC pathological diagnosis were selected, to collect heart blood samples of YUSD cases by ARVC pathological diagnosis( n=3), venous blood samples of immediate relatives with genetic relationship (case relatives, n=4) and control population without genetic relationship ( n=7). DNA was extracted for PCR amplification and sequencing of a total of 97 exons of the ARVC desmosomal protein genes plakophilin 2 (PKP2), desmoplakin (DSP), desmoglein 2 (DSG2), desmocollin 2 (DSC2), and junction plakoglobin (JUP), and the mutations of the 5 genes were analyzed in combination with the genetic family. Results:DSP gene mutations were found in all YUSD cases by ARVC pathological diagnosis and case relatives, and PKP2, DSG2, DSC2 and JUP genes mutations were found in 1 person each. The same person carried 1-3 genes mutations. DSP gene existed 4 exon mutation sites, and 1 of which was a newly discovered heterozygous synonymous mutation c.4014 C>A (p.A1338A). PKP2 gene existed 2 exon missense mutation sites in 1 YUSD case by ARVC pathological diagnosis, and 1 of which was a newly discovered heterozygous mutation c.739 G>C (p.G247R). One heterozygous missense mutation site c.799 G>A (p.A267T) of JUP gene was newly discovered, and the predictive value of protein function was 0.963, the possibility of abnormal changes in protein function was high. DSG2 and DSC2 genes each had one mutation site. However, no mutation was found in control population.Conclusions:Both YUSD cases by ARVC pathological diagnosis and case relatives carry ARVC desmosomal protein genes DSP, PKP2, DSG2, DSC2 and JUP mutations. There may be a certain pathogenesis relationship between YUSD and ARVC desmosomal protein gene mutations.
