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

Authors: Chun-Chi Lai; Yung-Hsin Yeh; Wen-Ping Hsieh; Chi-Tai Kuo; Wen-Ching Wang; Chia-Han Chu; Chiu-Lien Hung; +5 Authors

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

Abstract

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.To investigate the genetic background of a family affected by inherited CCD.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.Our results suggest that whole-exome sequencing is a feasible approach to identifying the candidate genes underlying inherited conduction diseases.

Keywords

Adult, Male, Science, DNA Mutational Analysis, Mutation, Missense, Cardiac Conduction System Disease, Heart Conduction System, Humans, Exome, Family, Aged, Brugada Syndrome, Aged, 80 and over, Q, R, Genetic Diseases, Inborn, Arrhythmias, Cardiac, Middle Aged, Lamin Type A, Pedigree, Protein Structure, Tertiary, Amino Acid Substitution, Medicine, Female, Research Article

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    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
12
Average
Top 10%
Top 10%
Green
gold