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Exome Sequencing Identifies Compound Heterozygous Mutations in SCN5A Associated with Congenital Complete Heart Block

Chuphong Thongnak1, Pornprot Limprasert2, Duangkamol Tangviriyapaiboon3

  • 1Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand; Excelence Center for Genomic Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Disease Markers
|December 27, 2016
PubMed

Insights

Genetic variants in the SCN5A gene were identified as the likely cause of complete heart block in a Thai family. These specific compound heterozygous variants were found only in the affected child, confirming their role in the condition.

Area of Science:

  • Genetics
  • Cardiology
  • Molecular Biology

Background:

  • Congenital heart block involves impaired electrical impulse transmission from the atrioventricular (AV) node to the ventricles.
  • Genetic variations affecting ion channels are a known cause of congenital heart block.
  • This study focuses on a Thai family with a history of complete heart block.

Purpose of the Study:

  • To identify causative genetic variants in a Thai family with complete heart block.
  • To investigate the role of ion channel gene mutations in congenital heart block.
  • To utilize whole exome sequencing for genetic variant discovery.

Main Methods:

  • Whole exome sequencing was performed on an affected child and an unaffected sibling from a three-generation Thai family.
  • Bioinformatics analysis was used to identify and filter genetic variants.
  • Candidate variants were validated, and segregation analysis was conducted on other family members.

Main Results:

  • Compound heterozygous variants (c.101G>A and c.3832G>A) were identified in the SCN5A gene.
  • A variant (c.28730C>T) was identified in the TTN gene.
  • The identified SCN5A variants were present exclusively in the affected child and not in unaffected family members.

Conclusions:

  • Compound heterozygous variants in the SCN5A gene are strongly implicated as the cause of complete heart block in this family.
  • The identified SCN5A variants demonstrate segregation with the disease phenotype within the family.
  • This finding highlights the importance of SCN5A gene mutations in congenital heart block etiology.

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