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PubMed 25010007


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Title: Whole-exome sequencing identifies Y1495X of SCN5A to be associated with familial conduction disease and sudden death.

Authors: Zhi-Ping Tan, Li Xie, Yao Deng, Jin-Lan Chen, Wei-Zhi Zhang, Jian Wang, Jin-Fu Yang, Yi-Feng Yang

Journal, date & volume: Sci Rep, 2014 , 4, 5616

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25010007


Abstract
SCN5A 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.