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- Title
Whole-Exome Sequencing to Identify a Novel LMNA Gene Mutation Associated with Inherited Cardiac Conduction Disease.
- 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; Tang, Chuan-Yi; Hsu, Lung-An
- Abstract
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.
- Subjects
NUCLEOTIDE sequence; LAMIN genetics; GENETIC mutation; HEART conduction system; GENETIC disorders; RARE diseases; DISEASES
- Publication
PLoS ONE, 2013, Vol 8, Issue 12, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0083322