Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
[Preprint]. 2024 Mar 20:rs.3.rs-3976548.
doi: 10.21203/rs.3.rs-3976548/v1.

Rapid Genome Sequencing Shows Diagnostic Utility In Infants With Congenital Heart Defects

Matthew D Durbin  1   2 , Lindsey R Helvaty  1 , Alyx Posorske  1 , Samuel Zhang  1 , Manyan Huang  3 , Ming Li  3 , Daniel Abreu  1 , Korre Fairman  4 , Gabrielle C Geddes  1 , Benjamin M Helm  1 , Benjamin J Landis  1   2 , Alexis McEntire  1 , Dana K Mitchell  1 , Stephanie M Ware  1   2
Affiliations

Rapid Genome Sequencing Shows Diagnostic Utility In Infants With Congenital Heart Defects

Matthew D Durbin et al. Res Sq. .

Abstract

Congenital heart disease (CHD) is the most common birth defect and a leading cause of infant mortality. CHD often has a genetic etiology and recent studies demonstrate utility in genetic testing. In clinical practice, decisions around genetic testing choices continue to evolve, and the incorporation of rapid genome sequencing (rGS) in CHD has not been well studied. Though smaller studies demonstrate the value of rGS, they also highlight the burden of results interpretation. We analyze genetic testing in CHD at two time-points, in 2018 and 2022-2023, across a change in clinical testing guidelines from chromosome microarray (CMA) to rGS. Analysis of 421 hospitalized infants with CHD demonstrated consistent genetic testing across time. Overall, after incorporation of rGS in 2022-2023, the diagnostic yield was 6.8% higher compared to 2018, and this pattern was consistent across all patient subtypes analyzed. In 2018, CMA was the most common test performed, with diagnostic results for CHD in 14.3%, while in 2022-2023, rGS was the most frequent test performed, with results diagnostic for CHD in 16.9%. Additionally, rGS identified 44% more unique genetic diagnoses than CMA. This is the largest study to highlight the value of rGS in CHD and has important implications for management.

PubMed Disclaimer

Conflict of interest statement

Competing Interest: Authors declare there is no competing financial interests in relation to the work desribed.

Similar articles

See all similar articles

References

    1. Thienpont B, Mertens L, de Ravel T, et al. Submicroscopic chromosomal imbalances detected by array-CGH are a frequent cause of congenital heart defects in selected patients. European heart journal. 2007;28(22):2778–2784. - PubMed
    1. Richards AA, Santos LJ, Nichols HA, et al. Cryptic chromosomal abnormalities identified in children with congenital heart disease. Pediatric research. 2008;64(4):358–363. - PubMed
    1. Breckpot J, Thienpont B, Peeters H, et al. Array comparative genomic hybridization as a diagnostic tool for syndromic heart defects. The Journal of pediatrics. 2010;156(5):810–817. e4. - PubMed
    1. Goldmuntz E, Paluru P, Glessner J, et al. Microdeletions and microduplications in patients with congenital heart disease and multiple congenital anomalies. Congenital heart disease. 2011;6(6):592–602. - PMC - PubMed
    1. Lalani SR, Shaw C, Wang X, et al. Rare DNA copy number variants in cardiovascular malformations with extracardiac abnormalities. European Journal of Human Genetics. 2013;21(2):173–181. - PMC - PubMed

Publication types

LinkOut - more resources