Wang Qian, Deng Yong, Fan Liang-Liang, Dong Yi, Zhang Ai-Qian, Liu Yu-Xing
Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, China.
Department of Nephrology, Xiangya Hospital of Central South University, Changsha, China.
BMC Cardiovasc Disord. 2024 Oct 1;24(1):527. doi: 10.1186/s12872-024-04204-3.
Primary electrical disorders (PEDs) are a group of cardiac rhythm abnormalities that occur in the absence of detectable structural heart disease and are a significant cause of sudden cardiac death (SCD). The initiation of cardiac muscle contraction and relaxation is orchestrated by the action potential (AP), generated through ionic changes across the membrane. Mutations in the AP-related gene CACNA2D1 have been identified as a causative factor for PED.
We recruited a Chinese family with a history of arrhythmia. The proband has experienced palpitations and chest tightness for over 40 years, with symptoms worsening over the past year. Whole exome sequencing (WES) was used to determine the genetic etiologies in this family.
A novel heterozygous missense mutation (NM_000722.3: c.1685G > C;p.G562A) of CACNA2D1 gene was detected. Genotyping of the proband's parents indicated that the arrhythmia phenotype in the proband was caused by a de novo mutation.
WES was utilized to explore the genetic etiology in a family with arrhythmia, leading to the identification of a novel mutation in the CACNA2D1 gene. This study not only expands the mutation spectrum of the CACNA2D1 gene but also contributes to genetic counseling and clinical diagnosis for this family.
原发性电紊乱（PEDs）是一组在无明显结构性心脏病情况下发生的心律失常，是心源性猝死（SCD）的重要原因。心肌收缩和舒张的启动由动作电位（AP）精心调控，动作电位通过跨膜离子变化产生。与动作电位相关的基因CACNA2D1中的突变已被确定为原发性电紊乱的一个致病因素。
我们招募了一个有心律失常病史的中国家庭。先证者有40多年的心悸和胸闷症状，在过去一年中症状加重。采用全外显子组测序（WES）来确定该家庭的遗传病因。
检测到CACNA2D1基因一个新的杂合错义突变（NM_000722.3:c.1685G＞C；p.G562A）。对先证者父母的基因分型表明，先证者的心律失常表型是由新发突变引起的。
利用全外显子组测序探索一个心律失常家庭的遗传病因，从而鉴定出CACNA2D1基因中的一个新突变。本研究不仅扩展了CACNA2D1基因的突变谱，也有助于该家庭的遗传咨询和临床诊断。
