Journals / The Anatolian Journal of Cardiology / 2018 / Cilt: 20 - Sayı: 1
Analysis of gene copy number variations in patients with congenital heart disease using multiplex ligation-dependent probe amplification
- Pages
- 9–15
- DOI
- —
Özet
Objective: At the molecular and cellular levels, heart development entails the precise orchestration of genetic events such as the interplay ofmaster transcriptional regulators, signaling pathways, and chromatin remodeling. Recent studies among patients with congenital heart disease(CHD) have shown the importance of recurrent copy number variations (CNVs) in a significant number of patients. Recurrent CNVs that spanseveral genes may affect other important organs, besides the heart. Because CHD may be the first presenting symptom in such patients, theanalysis of recurrent CNVs in the genomic regions containing genes associated with CHD in patients referring to cardiology clinics may lead toan early diagnosis and the treatment of extracardiac symptoms in these patients. In this study, we aimed to screen CNVs of genomic regionsincluding GATA4, NKX2-5, TBX5, BMP4, and CRELD1 genes and to analyse the 22q11.2 chromosomal region in apparently nonsyndromic patientswith cardiac septal defects.Methods: Genomic regions including GATA4, NKX2-5, TBX5, BMP4, and CRELD1 genes and the 22q11.2 chromosomal region were analyzed inapparently nonsyndromic 45 patients with cardiac septal defects using the MLPA P-311 A2 Congenital Heart Disease kit. Multiplex ligationdependentprobe amplification (MLPA) is an established technique for the detection of known CNVs. MLPA is substantially less expensive thanarray CGH and is relatively simple to use for clinicians without specific expertise in genomic technology; thus, MLPA could be used as a first-tierscreening assay.Results: We screened 45 patients with cardiac septal defects for CNVs using the MLPA P-311 A2 kit. We identified three CNVs (n=3/45, 6.66%)and three 22q11 deletions. The CNVs were confirmed using fluorescence in situ hybridization.Conclusion: Our study confirmed that the analysis of recurrent CNVs using the MLPA assay within pediatric cardiology clinics can led to an earlysyndrome diagnosis in nonsyndromic patients with CHD.