Genetic Etiology of Left-Sided Obstructive Heart Lesions: A Story in Development.

Journal Article (Journal Article;Review)

Congenital heart disease is the most common congenital defect observed in newborns. Within the spectrum of congenital heart disease are left-sided obstructive lesions (LSOLs), which include hypoplastic left heart syndrome, aortic stenosis, bicuspid aortic valve, coarctation of the aorta, and interrupted aortic arch. These defects can arise in isolation or as a component of a defined syndrome; however, nonsyndromic defects are often observed in multiple family members and associated with high sibling recurrence risk. This clear evidence for a heritable basis has driven a lengthy search for disease-causing variants that has uncovered both rare and common variants in genes that, when perturbed in cardiac development, can result in LSOLs. Despite advancements in genetic sequencing platforms and broadening use of exome sequencing, the currently accepted LSOL-associated genes explain only 10% to 20% of patients. Further, the combinatorial effects of common and rare variants as a cause of LSOLs are emerging. In this review, we highlight the genes and variants associated with the different LSOLs and discuss the strengths and weaknesses of the present genetic associations. Furthermore, we discuss the research avenues needed to bridge the gaps in our current understanding of the genetic basis of nonsyndromic congenital heart disease.

Full Text

Duke Authors

Cited Authors

  • Parker, LE; Landstrom, AP

Published Date

  • January 19, 2021

Published In

Volume / Issue

  • 10 / 2

Start / End Page

  • e019006 -

PubMed ID

  • 33432820

Pubmed Central ID

  • PMC7955312

Electronic International Standard Serial Number (EISSN)

  • 2047-9980

Digital Object Identifier (DOI)

  • 10.1161/JAHA.120.019006


  • eng

Conference Location

  • England