title: Whole-exome sequencing to identify a novel LMNA gene mutation associated with inherited cardiac conduction disease.
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.
  
  
  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.
authors.affiliation: Department of Computer Science, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Lai
authors.affiliation: First Cardiovascular Division, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
authors.forename: Yung-Hsin
authors.initials: YH
authors.lastname: Yeh
authors.affiliation: Institute of Statistics, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Wen-Ping
authors.initials: WP
authors.lastname: Hsieh
authors.affiliation: First Cardiovascular Division, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
authors.forename: Chi-Tai
authors.initials: CT
authors.lastname: Kuo
authors.affiliation: Institute of Molecular and Cellular Biology and Department of Life Sciences, National Tsing-Hua University, Hsinchu, Taiwan ; Biomedical Science and Engineering Center, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Wen-Ching
authors.initials: WC
authors.lastname: Wang
authors.affiliation: Biomedical Science and Engineering Center, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chia-Han
authors.initials: CH
authors.lastname: Chu
authors.affiliation: Institute of Molecular and Cellular Biology and Department of Life Sciences, National Tsing-Hua University, Hsinchu, Taiwan ; Biomedical Science and Engineering Center, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chiu-Lien
authors.initials: CL
authors.lastname: Hung
authors.affiliation: Department of Computer Science, National Tsing Hua University, Hsinchu, Taiwan ; Biomedical Science and Engineering Center, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chia-Yang
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: First Cardiovascular Division, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Tsai
authors.affiliation: Institute of Molecular and Cellular Biology and Department of Life Sciences, National Tsing-Hua University, Hsinchu, Taiwan.
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Lee
authors.affiliation: Department of Computer Science, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chuan-Yi
authors.initials: CY
authors.lastname: Tang
authors.affiliation: First Cardiovascular Division, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
authors.forename: Lung-An
authors.initials: LA
authors.lastname: Hsu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001145:Arrhythmias, Cardiac / Q000235:genetics*; D053840:Brugada Syndrome; D000075224:Cardiac Conduction System Disease; D004252:DNA Mutational Analysis; D059472:Exome; D005190:Family; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006329:Heart Conduction System / Q000002:abnormalities*; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D017434:Protein Structure, Tertiary
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A