Genetic Imbalances in Argentinean Patients with Congenital Conotruncal Heart Defects

Area of Science:

• Genetics
• Cardiology
• Genomic Medicine

Background:

• Congenital conotruncal heart defects (CCHD) are severe heart conditions affecting outflow tracts, occurring in ~1/1000 births.
• Chromosomal abnormalities and copy number variants (CNVs) are known risk factors for CCHD.
• Limited data exists on CCHD genetic factors in Latin American populations.

Purpose of the Study:

• To investigate chromosomal abnormalities, 22q11 deletions, and other genomic imbalances in Argentinean CCHD patients.
• To determine the frequency of these genetic factors in a local cohort of unknown etiology CCHD.
• To identify specific genomic alterations associated with CCHD in Argentina.

Main Methods:

• Analysis of 219 Argentinean patients with isolated or syndromic CCHD.
• Utilized cytogenetic studies, Multiplex-Ligation-Probe-Amplification (MLPA), and fluorescent in situ hybridization (FISH).
• Focused on detecting chromosomal abnormalities, 22q11 deletions, and other CNVs.

Main Results:

• No general cytogenetic abnormalities were detected.
• 22q11 deletion found in 23.5% of patients; 66% had isolated CCHD.
• Other clinically relevant CNVs identified include 22q11 duplication and deletions at 17p13.3, 4q35, and TBX1.
• Overall, 25.8% of CCHD patients exhibited disease-associated genomic imbalances.

Conclusions:

• Genomic imbalances, particularly 22q11 deletions, are significant contributors to CCHD in Argentinean patients.
• The study highlights the importance of genetic analysis in CCHD, even in cases without other major anomalies.
• Findings provide crucial insights into the genetic landscape of CCHD in Latin America.