To determine the probability of developing heart defect seguence method that degects seguence in dna nucleotide of responsible genes for most common heart defects / Монголын Анагаах Ухаан

ABSTRACT

BACKGROUND:Congenital heart defects (CHD) turn out to be the leading cause of infant mortality in their first yearafter infectious diseases. Per 1,000 infants, born with CHD, about 19-75 failed to survive. It revealsthe fact that CHD is a major cause of childhood mortality in worldwide. Beyond the progress ofmedicine and surgery, the cause of CHD is not fully defined. The majority of studies reveal that CHDis triggered by many factors, such as the genetic and environmental factors.Based on the evidences of the sequence of the human genome and advances in moleculartechnology, genetic factors play a major role. Per 100 newborninfants, they’re found one child, bornwith a CHD is concerned as a highly frequent incident for birth anomaly. Only 0.5% of these congenitaldefects enable to be inherited in accordance with Mendel’s genetic laws, which is associated withthe change and mutation of a single gene. Many found that most congenital anomalies dependupon mutation or change in multiple genes and other relevant factors. As a result of the progressivedevelopment of molecular biology in the past 20 years discovered a range of genes involved in fetusformation, development, growth and control of processes. In our country case, corrective surgeryfor CHD dominates among all cardiovascular surgery in Mongolia. Particularly, for all incidents donesome corrective surgery of congenital heart defects, atrial septal defect operation occupies 42.44%,in other word it is a substantial part of the CHDoperation (D.Tsegeenjav, 2009). Molecular geneticsstudy of infant born with heart defects and simultaneous anomaly of other organ system researchstill has not been done for Mongolian population. In many cases the diagnosis of CHD is delayeduntil their adulthood, which is a research gap to address without further delay and the finding mustbe applied in practice in the near future.GOALThe aim of the research is to conduct a molecular genetic study of children, born with CHD andcombined abnormalities of other organs and systems, identify gene lesion, location and characteristicsof mutations, pathogenetic mechanism of congenital defects and anomalies among the Mongolianpopulation.RESULT:For this study, there are 118 patients, with congenital heart disease, received surgical treatmentin the cardiovascular department of III central state hospital named P.N. Shastin, involved afterconfirmed diagnosis through objective and instrumental investigations (ECG, Fluoroscopy, EchoKG).The 118 healthy family members of patients sampled as a control group. According to the diagnosisof patients with congenital heart defect, such as atrial septal defects-95 (81.2% ± 3.6), ventricularseptal defects-17 (14.5% ± 3.3), patent ductusarteriosus- 2 (1.7± 0 .0%) have combined severedefects - 4 (3.3% ± 1.0). Out of 118 patients with congenital heart defects, 32.2% (38 patients)was male, whereas women accounted for 67.8% (80 patients) with average age of 22, 3 ± 12.9(minimum 1.0 year, maximum 51 year). These comprised 42.4% in 1-17 years old (average age10 ± 5.27) and 57.6% in 18-51 years old (average age 31 ± 9.54). The 33.9% ± 4.4 (40 patients) of operated patients responded the questionnaire that they have a hereditary heart defect. Shortnessof breath, heart pain, and recurrent pneumonia were the main complaints of patients with CHDthat significantly authentic to statistical probability. From the taken 118 blood samples, 95 werediagnosed ASD, in 7 diagnosed VSD, in 2 diagnosed PDA, in 4 diagnosed combined defects. Forthe 95 samples, we decided to examine the ASD associated GATA4, TBX5gene. It draws attentionto the fact that 81.2% of all congenital heart defects found only ASD. To examine the ASD genes inthe sample, the following changes have occurred. The study found 8 variants of mutations formingASD. It includes on exon 1 Gly 93 Ala (c.278G> C), on exon 1 P163S (c.487C>T).CONCLUSIONS:1. Patients with ASD alone occupy 81,2% of all heart defects in our study.2. For the samples of ASD, the study found 8 different mutations of GATA4.3. In the sample of blood not found TBX5 gene mutation.4. In the samples, one patient with dextrocardiasitusinvertus was combined with congenital heartdefects found E359Xfs (c.1075delG) deletion variation on exon3.