Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Genome Med. 2020 Jan 15;12(1):9. doi: 10.1186/s13073-019-0709-8.

De novo variants in exomes of congenital heart disease patients identify risk genes and pathways.

Author information

1
Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
2
St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY, USA.
3
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, USA.
4
Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
5
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
6
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
7
Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. yuval.itan@mssm.edu.
8
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. yuval.itan@mssm.edu.

Abstract

BACKGROUND:

Congenital heart disease (CHD) affects ~ 1% of live births and is the most common birth defect. Although the genetic contribution to the CHD has been long suspected, it has only been well established recently. De novo variants are estimated to contribute to approximately 8% of sporadic CHD.

METHODS:

CHD is genetically heterogeneous, making pathway enrichment analysis an effective approach to explore and statistically validate CHD-associated genes. In this study, we performed novel gene and pathway enrichment analyses of high-impact de novo variants in the recently published whole-exome sequencing (WES) data generated from a cohort of CHD 2645 parent-offspring trios to identify new CHD-causing candidate genes and mutations. We performed rigorous variant- and gene-level filtrations to identify potentially damaging variants, followed by enrichment analyses and gene prioritization.

RESULTS:

Our analyses revealed 23 novel genes that are likely to cause CHD, including HSP90AA1, ROCK2, IQGAP1, and CHD4, and sharing biological functions, pathways, molecular interactions, and properties with known CHD-causing genes.

CONCLUSIONS:

Ultimately, these findings suggest novel genes that are likely to be contributing to CHD pathogenesis.

KEYWORDS:

Congenital heart disease; De novo variants; Enrichment analysis; Pathway; Trios

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center