Akademik Veri Yönetim Sistemi
European Human Genetics Conference Hybrid Conference Milan, Italy May 24–27, 2025, Milan, İtalya, 24 - 27 Mayıs 2025, ss.7038, (Özet Bildiri)
Background:Congenital heart disease (CHD) is a genetically based disorder that affects approximately 1% of live births worldwide. Whole exome sequencing (WES) studies help identify genetic variants that may correlate with the clinical presentation of CHD
Material and Methods:DNA was isolated from peripheral blood of 4 index cases and their family members. WES was performed on the index cases. Variants identified as pathogenic/likely pathogenic or variants of uncertain significance were evaluated.
Results:Variants were detected in 4 CHD cases with extracardiac anomalies whose microarray-based comparative genomic hybridization analysis (aCGH) was normal: Case 1 (6 months,male), heterozygous MED13L c.3613C>T, case 2 (5 months,female), heterozygous NOTCH1 nonsense c.3319C>T and TBX1 missense c.1347C>G; case 3 (neonatal,male), homozygous DCAF6 nonsense c.649C>T; case 4 (prenatal,male) heterozygous GATA4 frameshift c.680del and SMAD2 nonsense c.559del. The MED13L and GATA4 variants were confirmed by Sanger sequencing and segregation analysis revealed that they were de novo, classified as “likely pathogenic” by ACMG, and were consistent with the clinical phenotype.Validation and segregation analysis for other variants are ongoing.
Conclusion:The study suggests that identifying causal genetic variants in the etiology of CHD could help predict disease prognosis and provide personalized treatments. In the prenatal period, genetic counseling can be provided to families, and prenatal and preimplantation diagnosis options can be offered in high-risk pregnancies. Studies reveal rare mutations in multiple genes in cases of CHDs may contribute to their development due to their synergistic nature, underscoring the need for further research to address the genetic complexity of this common and genetically heterogeneous disease.