cnv analysis using multiplex ligation-dependent probe amplification in iranian families with non-syndromic congenital heart defects: early diagnosis of non-syndromic patients

Background and aims: congenital heart defects (chd) are the most common type of congenital disability. copy number variations (cnvs) have been found as one of the genetic etiology of nonsyndromic chd, and researchers have detected several pathogenic cnvs in patients with cardiac defects. materials and methods: in the present study, 70 patients with familial (20 patients) and sporadic (50 patients) non-syndromic chd were evaluated to find whether cnvs in the gata4, nkx2-5, tbx5, crel, bmp4 genes, and 22q11.2 region contribute to the pathogenesis of non-syndromic chd. we have used the multiplex ligation-dependent probe amplification (mlpa) technique as a molecular method to identify cnvs in predefined loci. results: normal mlpa results were demonstrated for gata4, nkx2-5, tbx-5, creld, and bmp4 genes for all sporadic and familial cases. however, we found three patients with imbalances for the 22q11.2 region. one patient with 22q11.2 deletion showed tetralogy of fallot, and the other had ventricular septal defects/ pulmonary atresia/ multiple aortopulmonary collateral arteries. a duplication of the 22q11.2 region was detected in one patient with patent ductus arteriosus. conclusion: identifying genomic imbalances in 6% of the nonsyndromic sporadic patients indicates that recurrent cnvs could be associated with non-syndromic chd. it seems that it is the first cnv analysis using mlpa carried out in iranian patients with cardiac defects. we suggest that 22q11.2 imbalances should be considered in patients with cardiac lesions to provide an accurate diagnosis and appropriate genetic counseling in affected families.