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Analysis of Congenital Heart Defects in Mouse Embryos Using Qualitative and Quantitative Histological Methods
Published on: March 10, 2020
Human Genetics of Ventricular Septal Defect
Andreas Perrot1, Silke Rickert-Sperling2
1Experimental and Clinical Research Center, a Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Berlin, Germany.
Insights
Ventricular septal defects (VSDs) are common congenital heart diseases with complex genetic causes. Recent advances reveal significant genetic heterogeneity, including chromosomal abnormalities and gene mutations, in VSD patients.
Area of Science:
- Genetics
- Cardiology
- Developmental Biology
Background:
- Ventricular septal defects (VSDs) are a leading type of congenital heart disease (CHD), comprising up to 40% of all cardiac malformations.
- VSDs can occur independently or alongside other congenital anomalies, affecting individuals and families.
- The genetic basis of VSDs is known to be complex and highly diverse.
Purpose of the Study:
- To explore the genetic heterogeneity of VSDs.
- To review recent advancements in understanding the genetic causes of VSDs.
- To discuss various genetic factors contributing to VSD development.
Main Methods:
- Review of literature on VSD genetics.
- Analysis of chromosomal abnormalities (aneuploidy, structural variations).
- Identification of point mutations in key cardiac genes (e.g., NKX2-5, GATA4).
- Application of high-resolution techniques like comparative genomic hybridization (CGH) to detect copy number variations (CNVs).
Main Results:
- Identified a broad spectrum of genetic factors associated with VSDs.
- Confirmed the involvement of both chromosomal abnormalities and specific gene mutations.
- Highlighted the role of cardiac transcription factors and signaling molecules.
- Discovered numerous copy number variations in VSD patients using advanced genomic methods.
Conclusions:
- VSDs exhibit extraordinary genetic heterogeneity.
- Understanding the diverse genetic underpinnings is crucial for diagnosis and management.
- Ongoing research utilizing high-resolution genomic techniques continues to uncover new genetic associations.
Abstract:
Ventricular septal defects (VSDs) are recognized as one of the commonest congenital heart diseases (CHD), accounting for up to 40% of all cardiac malformations, and occur as isolated CHDs as well as together with other cardiac and extracardiac congenital malformations in individual patients and families. The genetic etiology of VSD is complex and extraordinarily heterogeneous. Chromosomal abnormalities such as aneuploidy and structural variations as well as rare point mutations in various genes have been reported to be associated with this cardiac defect. This includes both well-defined syndromes with known genetic cause (e.g., DiGeorge syndrome and Holt-Oram syndrome) and so far undefined syndromic forms characterized by unspecific symptoms. Mutations in genes encoding cardiac transcription factors (e.g., NKX2-5 and GATA4) and signaling molecules (e.g., CFC1) have been most frequently found in VSD cases. Moreover, new high-resolution methods such as comparative genomic hybridization enabled the discovery of a high number of different copy number variations, leading to gain or loss of chromosomal regions often containing multiple genes, in patients with VSD. In this chapter, we will describe the broad genetic heterogeneity observed in VSD patients considering recent advances in this field.
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