Identification of rare variants of DSP gene in sudden unexplained nocturnal death syndrome in the southern Chinese Han population.
Identification of rare variants of DSP gene in sudden unexplained nocturnal death syndrome in the southern Chinese Han population.
复制标题
中国南方汉族人群不明原因夜间死亡综合征中 DSP 基因罕见变异的鉴定。
DOI：
10.1007/s00414-015-1275-2
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发表时间：
2016-03
影响因子：
2.1
通讯作者：
Cheng J
中科院分区：
文献类型：
--
作者：
Zhao Q;Chen Y;Peng L;Gao R;Liu N;Jiang P;Liu C;Tang S;Quan L;Makielski JC;Cheng J
不明原因夜间猝死综合征（SUNDS）是一个令法医病理学家和临床医师都十分困惑的疾病。桥粒斑蛋白（DSP）基因是第一个与致猝死性右室心肌病（ARVC）相关的桥粒基因。为了确定中国南方汉族人群SUNDS中DSP基因的遗传变异，我们使用下一代测序（NSG）和直接桑格测序技术对40例散发性SUNDS患者、16例Brugada综合征（BrS）患者和2例早期复极综合征（ERS）患者的DSP基因进行了遗传筛查。在11例病例中共检测到DSP基因的10种遗传变异，包括两种新的错义突变（p.I125F和p.D521A）和8种先前报道的罕见变异。在报告的8种变异中，2种以前被认为是致病性的（p.Q90R和p.R2639Q），3种被计算机预测为致病性的（p.R315C、p.E1357D和p.D2579H），其余3种被预测为良性的（p.N1234S、p.R1308Q和p.T2267S）。这是首次报道中国人SUNDS和Brugada综合征的DSP基因筛查。我们的研究结果表明，DSP突变有助于一些SUNDS受害者的遗传原因，并可能是Brugada综合征的一个新的易感基因。
Sudden unexplained nocturnal death syndrome (SUNDS) is a perplexing disorder to both forensic pathologists and clinic physicians. Desmoplakin (DSP) gene was the first desmosomal gene linked to arrhythmogenic right ventricular cardiomyopathy (ARVC) which was associated with sudden death. To identify the genetic variants of the DSP gene in SUNDS in the southern Chinese Han population, we genetically screened the DSP gene in 40 sporadic SUNDS victims, 16 Brugada syndrome (BrS) patients and 2 Early Repolarization syndrome (ERS) patients using Next Generation Sequencing (NSG) and direct Sanger sequencing. A total of 10 genetic variants of the DSP gene were detected in 11 cases, comprised of two novel missense mutations (p.I125F and p.D521A) and eight previously reported rare variants. Of eight reported variants, two were previously considered pathogenic (p.Q90R and p.R2639Q), three were predicted in silico to bepathogenic (p.R315C, p.E1357D and p.D2579H), and the rest three were predicted to be benign (p.N1234S, p.R1308Q and p.T2267S). This is the first report of DSP genetic screening in Chinese SUNDS and Brugada syndrome. Our results implies that DSP mutations contribute to the genetic cause of some SUNDS victims and maybe a new susceptible gene for Brugada syndrome.