No evidence for mosaic pathogenic copy number variations in cardiac tissue from patients with congenital heart...

Area of Science:

• Genetics
• Cardiology
• Developmental Biology

Background:

• Congenital heart malformations (CHMs) are common birth defects.
• The genetic basis of CHMs is complex, involving both constitutional and potentially mosaic alterations.
• Investigating mosaic copy number variations (CNVs) in affected tissues is crucial for understanding CHM etiology.

Purpose of the Study:

• To determine the presence and frequency of pathogenic CNVs in mosaic form within cardiac tissue of patients with CHMs.
• To compare the genetic landscape of cardiac tissue with peripheral blood for CNV detection.

Main Methods:

• Cardiac tissue and blood samples were collected from 23 patients with CHMs.
• Array comparative genomic hybridization (array CGH) was employed to screen for mosaic gene dose alterations specifically in cardiac tissue.
• Analysis focused on detecting CNVs present in a subset of cells within the cardiac tissue.

Main Results:

• No evidence of mosaic CNVs was detected in the cardiac tissue samples using array CGH.
• Pathogenic CNVs, present in both cardiac tissue and blood, were identified in 2 out of 23 patients (9%).
• Several constitutional CNVs of uncertain clinical significance were also identified.

Conclusions:

• Mosaic pathogenic CNVs are not a common cause of congenital heart malformations.
• Constitutional pathogenic CNVs are confirmed as significant contributors to CHMs.
• This study provides the first investigation into mosaic CNVs in heart tissue versus peripheral blood for CHM patients.