A novel nonsense mutation in LMNA gene identified by Exome Sequencing in an atrial fibrillation family

Eur J Med Genet. 2016 Aug;59(8):396-400. doi: 10.1016/j.ejmg.2016.06.006. Epub 2016 Jun 30.

Abstract

Genetic factor plays an important role in cardiac arrhythmias. Several loci have been identified associated with this disease. However, they only explained parts of it and more genes and loci remain to be identified. In present study, we recruited a four generation family from the north of China. Four members of this family were diagnosed with atrial fibrillation by electrocardiogram (ECG). We used Exome Sequencing and Sanger sequencing to explore the candidate mutation for cardiac arrhythmia in this family. A nonsense mutation (c.G1494A, p.Trp498Ter) in the LMNA gene were identified as the candidate mutation. This variant is a novel mutation and has not yet been reported for any actual databases. This novel mutation co-segregated exactly with the disease in this family. Meanwhile, it was not detected in 524 control subjects of matched ancestry. According to structural model prediction, the mutation is expected to affect the Lamin Tail Domain (LTD) of lamin A/C protein. So the nonsense mutation discovered in the family probably was a novel mutation associated with familial atrial fibrillation. This discovery expands the mutation spectrum of LMNA and indicates the importance of LMNA in AF.

Keywords: Atrial fibrillation; Exome Sequencing; LMNA; Mutation.

MeSH terms

  • Amino Acid Sequence
  • Atrial Fibrillation / diagnosis*
  • Atrial Fibrillation / genetics*
  • Codon, Nonsense*
  • Computational Biology / methods
  • DNA Mutational Analysis
  • Electrocardiography
  • Exome
  • Family
  • Female
  • Genetic Association Studies
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lamin Type A / chemistry
  • Lamin Type A / genetics*
  • Male
  • Models, Molecular
  • Pedigree
  • Protein Conformation
  • Structure-Activity Relationship

Substances

  • Codon, Nonsense
  • Lamin Type A