Determining genetic variants in children and adolescents suffering from Tetralogy of Fallot with a positive family history: methodology

BACKGROUND AND AIM: Congenital heart disease (CHD) affects close to 1% of all live births and is considered as the main reason for morbidity and mortality in early childhood. In this study, we aimed to investigate molecular genetic factors associated with Tetralogy of Fallot (TOF), using high throughput technologies in the consanguineous families with at least two affected individuals. METHOD: This family study started from March 2017 to May 2019, in the pediatric cardiovascular research center, Cardiovascular Research Institute, Isfahan, Iran. Families with consanguineous marriage who had at least two patients in pedigree were invited to attend. Genomic DNA was extracted from peripheral blood lymphocytes of the patient and samples were investigated for variations such as deletion or duplication in the genome, using single nucleotide polymorphism array (SNP array). In the next step, if the SNP array was negative, the next generation sequencing (NGS) was performed in the probands. The raw data was analyzed and filtered to identify the genetic cause of the disease. RESULTS: In this study, total five families were evaluated. All affected and unaffected individuals of each family included in the pedigree. Fourteen subjects, 9 males and 5 females, 8.92±6.21 years old were included. The prevalence of consanguineous marriage was 92.2% among parents, 71.4% among maternal grandparents and 28.6% among paternal grandparents. Almost, 64.3% of our participants had a sibling with a similar disease. The prevalence of Atrial Septal Defect (ASD), Ventricular Septal Defect (VSD), and arrhythmia and TOF was 7.1%. CONCLUSION: We found some families with two or more CHD cases and with high rate of consanguineous marriage, having a genetic predisposition. In the next step, high throughput techniques such as NGS and SNP-array was performed in order to find any genetic variation. Functional study will be done, to confirm and determine the role of the identified variants in the function of genes involved in disease phenotype. (www.actabiomedica.it)