Molecular genetic mechanisms of congenital heart disease

Area of Science:

• Genetics
• Developmental Biology
• Pediatrics

Background:

• Congenital heart disease (CHD) impacts approximately 1% of live births globally.
• A definitive etiological cause for CHD is identified in only about 50% of affected individuals.
• Known causes include chromosomal abnormalities, copy-number variations, single-gene mutations, and environmental exposures.

Purpose of the Study:

• To summarize established genetic contributors to CHD.
• To discuss emerging complex genetic mechanisms that may explain the etiology of CHD cases lacking a molecular diagnosis.
• To address the heterogeneity and incomplete penetrance observed in CHD phenotypes.

Main Methods:

• Review of current literature on CHD genetics.
• Analysis of findings from high-throughput sequencing of large CHD patient cohorts.
• Integration of knowledge on the molecular regulation of cardiac morphogenesis.

Main Results:

• Numerous genes associated with CHD have been identified through advanced sequencing techniques.
• The limitations of a purely monogenic model for explaining CHD are highlighted.
• Complex genetic mechanisms are increasingly recognized as crucial in CHD etiology.

Conclusions:

• Existing genetic knowledge does not fully account for the complexity and variability of CHD.
• Emerging concepts in complex genetics offer potential explanations for previously undiagnosed CHD cases.
• Further research into multifactorial genetic underpinnings is essential for a comprehensive understanding of CHD.