Detection of the Copy Number Variants of Genes in Patients with Familial Cardiac Diseases by Massively Parallel Sequencing

Mol Diagn Ther. 2023 Jan;27(1):105-113. doi: 10.1007/s40291-022-00624-z. Epub 2022 Dec 1.

Abstract

Introduction: The implication of copy number variations in familial heart disease is known, although in-depth knowledge is lacking; hence, more studies are needed to further our understanding. Massively parallel sequencing, thanks to its recent surge in use, is emerging as a valid tool for the detection of this type of variant, through the use of appropriate software.

Methods: We conducted a study with 182 patients diagnosed with mendelian cardiovascular diseases who underwent sequencing using a cardiac gene panel and then a specific calling process for copy number variations (CNVs) with ExomeDepth software, which provides us with a Bayes factor (BF), a score of the probability that a CNV detected is true.

Results: After a rigorous CNV prioritization process, we confirmed the variants obtained by MLPA or SNP-based array, finding three real CNVs in five individuals in the MYH11, FBN1 and PDMI7 genes.

Conclusion: The confirmed CNVs present in all cases BF values > 60, thus establishing a threshold to consider real CNVs in the calling process carried out by ExomeDepth on our gene panel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • DNA Copy Number Variations*
  • Heart Diseases*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Software