Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
Department of Cardiology, Institute of Cardiovascular Disease, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
Life Sci. 2019 Feb 15;219:74-81. doi: 10.1016/j.lfs.2018.12.062. Epub 2019 Jan 3.
Progressive cardiac conduction disease (PCCD) is a rare heart disease that usually shows familial inheritance. Potential genetic risk factors for PCCD have been mostly limited to genes that encode ion channels, cardiac transcription factors, T-box transcription factors, gap junction proteins, energy metabolism regulators and structural proteins.
Subjects in the present study came from a family who exhibited the autosomal dominant inheritance of PCCD. The primary proband had syncope and an electrocardiogram typical for PCCD, which started in the left bundle branch block, and passed to the atrioventricular block. The patient received a permanent pacemaker in 2013. Pathogenic mutations in the proband's family were identified using whole-exome sequencing and Sanger sequencing.
The results for the family members were verified using Sanger sequencing, while the results for healthy unrelated individuals were verified using SNaPShot. All patients in the family shared two adjacent missense mutations in the preprodynorphin (PDYN) gene (c.581A > T, c.580G > C; p.D194L).
The PDYN double mutation c.581A > T and c.580G > C (p.D194L) may be linked to the onset of familial PCCD. The effects of these mutations on electrophysiology require further investigation.
进行性心脏传导疾病（PCCD）是一种罕见的心脏病，通常表现为家族遗传。PCCD 的潜在遗传危险因素大多局限于编码离子通道、心脏转录因子、T 盒转录因子、缝隙连接蛋白、能量代谢调节剂和结构蛋白的基因。
本研究的受试者来自一个家族，该家族表现出 PCCD 的常染色体显性遗传。主要先证者出现晕厥和心电图呈 PCCD 典型表现，始于左束支传导阻滞，继而发展为房室传导阻滞。该患者于 2013 年植入永久性起搏器。通过全外显子组测序和 Sanger 测序鉴定先证者家系中的致病突变。
通过 Sanger 测序对家系成员进行验证，而对健康无关个体进行验证则使用 SNaPShot。家系中所有患者均共享前脑啡肽原（PDYN）基因中的两个相邻错义突变（c.581A>T，c.580G>C；p.D194L）。
PDYN 双突变 c.581A>T 和 c.580G>C（p.D194L）可能与家族性 PCCD 的发病有关。这些突变对电生理学的影响需要进一步研究。
