Investigation of copy number variation in children with conotruncal heart defects

Abstract

BackgroundCongenital heart defects (CHD) are the most prevalent group of structural abnormalities at birth and one of the main causes of infant morbidity and mortality. Studies have shown a contribution of the copy number variation in the genesis of cardiac malformations.ObjectivesInvestigate gene copy number variation (CNV) in children with conotruncal heart defect.MethodsMultiplex ligation-dependent probe amplification (MLPA) was performed in 39 patients with conotruncal heart defect. Clinical and laboratory assessments were conducted in all patients. The parents of the probands who presented abnormal findings were also investigated.ResultsGene copy number variation was detected in 7/39 patients: 22q11.2 deletion, 22q11.2 duplication, 15q11.2 duplication, 20p12.2 duplication, 19p deletion, 15q and 8p23.2 duplication with 10p12.31 duplication. The clinical characteristics were consistent with those reported in the literature associated with the encountered microdeletion/microduplication. None of these changes was inherited from the parents.ConclusionsOur results demonstrate that the technique of MLPA is useful in the investigation of microdeletions and microduplications in conotruncal congenital heart defects. Early diagnosis of the copy number variation in patients with congenital heart defect assists in the prevention of morbidity and decreased mortality in these patients.

Prenatal diagnosis of submicroscopic chromosomal aberrations in fetuses with ventricular septal defects by chromosomal microarray‐based analysis

“…Campos et al reported a newborn with severe coarctation of the aorta, patent ductus arteriosus, an atrial septal defect, and several VSDs identified by echocardiography, duodenal atresia, left appendix, constipation, feeding difficulties, failure to thrive, hypertonia, and neuropsychomotor development delay; this child died at the age of 4 months. 31 Case 25 had a 23.5-Kb deletion in chromosome 16p13.3 that contained two OMIM genes, HBA1 and HBA2, which are associated with Hemoglobin H disease. 32 We observed three (5.8%) cases of VOUS.…”

Major Contribution of Genomic Copy Number Variation in Syndromic Congenital Heart Disease: The Use of MLPA as the First Genetic Test

“…The rates of diagnosis in the various studies are highly variable, from 3.2 to 33.3% [Sørensen et al, 2012;Wang et al, 2013;Campos et al, 2015], which is due to the technique used and the method of selecting patients. In our case, there is a bias towards more severe patients since all of them were syndromic.…”

“…Some researchers have investigated the contribution of chromosomal alterations in CHD patients using the MLPA technique; the results ranged from 3.2-33.33% and showed to be highly dependent on the selection of patients and the type of kit used [Sørensen et al, 2012;Wang et al, 2013;Campos et al, 2015].…”

Copy-number variant analysis of classic heterotaxy highlights the importance of body patterning pathways

“…The third CNV, a deletion in 8p23.2, did not encompass any genes. In addition to Fakhro et al (2011), another CNV investigation identified a duplication in 8p23.2 in an individual with tetralogy of Fallot (Campos et al 2015). In addition to the deletion in 8p23.2, this case had three exonic heterozygous mutations in DNAH11 (Table 1), all with unknown significance.…”