Whole-Exome Sequencing to Identify a Novel LMNA Gene Mutation Associated with Inherited Cardiac Conduction Disease: e83322

• Published in: PloS one 2013-12, Vol.8 (12)
• Main Authors: Lai, Chun-Chi, Yeh, Yung-Hsin, Hsieh, Wen-Ping, Kuo, Chi-Tai, Wang, Wen-Ching, Chu, Chia-Han, Hung, Chiu-Lien, Cheng, Chia-Yang, Tsai, Hsin-Yi, Lee, Jia-Lin
• Format: Article
• Language: English
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0083322

Background Inherited cardiac conduction diseases (CCD) are rare but are caused by mutations in a myriad of genes. Recently, whole-exome sequencing has successfully led to the identification of causal mutations for rare monogenic Mendelian diseases. Objective To investigate the genetic background of a family affected by inherited CCD. Methods and Results We used whole-exome sequencing to study a Chinese family with multiple family members affected by CCD. Using the pedigree information, we proposed a heterozygous missense mutation (c.G695T, Gly232Val) in the lamin A/C (LMNA) gene as a candidate mutation for susceptibility to CCD in this family. The mutation is novel and is expected to affect the conformation of the coiled-coil rod domain of LMNA according to a structural model prediction. Its pathogenicity in lamina instability was further verified by expressing the mutation in a cellular model. Conclusions Our results suggest that whole-exome sequencing is a feasible approach to identifying the candidate genes underlying inherited conduction diseases.