الفهرس 
Congenital Heart DiseaseOnly 14 pages are availabe for public view
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Abstract
Congenital heart defects (CHDs) are most common of all birth defects. CHD may be an isolated malformation or may be part of a syndrome. One of the common syndromes associated with CHDs includes DiGeorge Syndrome (DGS) or 22q11.2 deletion syndrome.
Aberration in the 22q11chromosomal region is one of the most common chromosomal abnormalities in humans and lead to complex phenotypes that make them an important public health problem.
The prevalence of 22q11.2 microdeletion syndrome is approximately 1 in 4000 births and accounts for 5 – 30% of all heart defects. The clinical features associated with 22q11.2 deletion include contruncal cardiac defect, thymic hypoplasia, cleft palate and hypocalcemia.
Cytogenetically del22q11.2 syndrome is when the affected individual carries deletion only in one of chromosome 22. So it is presumed to be gene haploinsufficiency syndrome.
Most people with 22q11.2 deletion syndrome are missing about 3 million base pair on one copy of chromosome 22 in each cell. The deletion occurs near the middle of the chromosome at location designated as q11.2. This region contains 30 to 40 genes. The particular lost gene is thought to be responsible for many characteristics features of 22q11.2. In most cases the deletion occurs de novo but in about 10% cases it is inherited form parents affected mildly.
This study aims to detect the loss of heterozygosity in 22q11 based microsatellite markers in congenital heart diseases for affected children and their parents, correlate the extinct haplotypes of deletion boundaries with CHDs kinds and provide the preliminary protocol in early diagnosis of 22q11 microdeletion for CHDs patients.
This case-control study was done on patients referred from both Clinical Genetics Clinic at National Research Centre Egypt and Banha university hospitals, in the period starting from December 2015 to December 2016.
The present study comprised of 20 children suffered from congenital heart diseases [Their median age was 18.5months, they were 7 males (35%) and 13 females (65%)] and their parents. In addition to 20 healthy control (12 females and 8 males with age range from 6 months to 9 years) and their parents as control group.
All patients and parents were subjected to the following: Full medical history including age, gender, family history,full clinical examination,ECG and Echocardiography and molecular study of several markers covering 3Mb on 22q11 region.
Genetic analysis: 22q11.2 genetic analysis has been performed in all individuals subjected to this study and the two groups were compared regarding the results of the genetic polymorphism.
Our results were listed as follow:
- Three cases had consanguinity (15%), whereas, 17 cases showed no consanguinity (85%).
- All cases had CHD (2 with TOF, 2 with TGA,8 with VSD,8 with ASD and3 with PS) 15% showed dysmorphic features and 1 case had MR (5%).
- Using a set of three known consecutive high polymorphic short tandem repeat markers along the 22q11.21 region; D22S941, D22S944 and D22S264 loci. We found loss of heterozygosity in D22S941 locus in 2 out of 20 families (10%) with 2 offspring affected by ASD combined with PS and TOF respectively. no LOH found in D22S944 and D22S264 loci either in affected cases or control group and no LOH found in D22S941 in the control group. Also we observed that D22S944 locus prone to be less allele diversity than D22S941 and D22S264 loci.
- Only 2 cases showed D22S941 LOH. The first case was male patient, aged 15 months, no consanguinity. The patient had ASD, PS and dysmorphic features. The band size was 304 bp, that of father was 304 bp and of mother was 291 and 271.The second cases was male, ages 24 months no consanguinity. The patient had TOF. The band size was 299 bp, that of father was 299 bp and of mother was 290 and 271.
- No significant differences were found in number of bands of D22S264,D22S941and D22S944 microsatellite markers in the children and their parents under study.
Conclusion:-
The study found loss of heterozygosity in D22S941 locus in 10% of children affected by ASD combined with PS and TOF.