Researchers identify a novel mutation through whole-exome sequencing

Reviewed by James Ives, M.Psych. (Editor)Jun 27 2020

In a new publication from Cardiovascular Innovations and Applications; Yafei Zhai, Jinxin Miao, Ying Peng, Guangming Fang, Chuchu Wang, Yaohe Wang, Xiaoyan Zhao and Jianzeng Dong from Zhengzhou University, Zhengzhou, P. R. China, Henan University of Chinese Medicine, Zhengzhou, P. R. China and Capital Medical University, Beijing, China consider digenic mutation of KCNH2 c.1898A > C and JUP c.916dupA, in a Chinese family with Long QT Syndrome.

Long QT syndrome (LQTS), caused by an ion channel-related gene mutation, is a malignant heart disease with a clinical course of a high incidence of ventricular fibrillation and sudden cardiac death in the young.

Mutations in KCNH2 (which encodes potassium voltage-gated channel subfamily H member 2) are responsible for LQTS in many patients.

The authors report the novel mutation c.1898A>C in KCNH2 in a Chinese family with LQTS through whole-exome sequencing. The c.916dupA mutation in JUP (which encodes junction plakoglobin) was also discovered.

Mutations in JUP were found to be associated with arrhythmogenic right ventricular cardiomyopathy. The double mutation in the proband may help explain severe clinical manifestations, such as sudden cardiac death at an early age.

Sequencing for the proband's family members revealed that the KCNH2 mutation descends from the paternal line, while the mutation in JUP came from the maternal line.

The data provided in this study may help expand the spectrum of LQTS-related KCNH2 mutations and add support to the genetic diagnosis and counselling of families affected by malignant arrhythmias.