• Zhi-Ping Tan, Li Xie, Yao Deng, Jin-Lan Chen, Wei-Zhi Zhang, Jian Wang, Jin-Fu Yang, and Yi-Feng Yang.
• 1] Department of Cardiothoracic Surgery, the Second Xiangya Hospital of Central South University, Changsha, Hunan Province 410011, China [2] Clinical Center for Gene Diagnosis and Therapy of State Key Laboratory of Medical Genetics, the Second Xiangya Hospital of Central South University, Changsha, Hunan Province 410011, China.
• Sci Rep. 2014 Jul 10; 4: 5616.

AbstractSCN5A mutations have been reported to underlie a variety of inherited arrhythmias, while the complex overlapping phenotype, especially with congenital heart disease (CHD), is rarely reported. The 48-year-old proband underwent a recent syncope during rest. A CHD (tetralogy of Fallot) and conduction disease was revealed by echocardiogram and ultrasonic cardiogram examination. We combined whole-exome sequencing (WES) and bioinformatics strategies to identify the pathogenic gene for this autosomal-dominant cardiac conduction disease (CCD) in a multi-generation pedigree. We examined four members of this family, including three affected and one unaffected. A novel nonsense mutation (Y1495X) in SCN5A was identified in the affected family members. This mutation is predicted to generate a truncated SCN5A protein, which could result in the loss of sodium current, a defined mechanism of SCN5A related arrhythmias. Our study provides evidence that WES is a highly effective approach for genetic analyses of rare clinical phenotypes. Our study also offers accurate genetic testing information for those yet clinically negative relatives.

33 keywords...

hide…