
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.
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
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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