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HLA antigens in multiplex families with isolated congenital heart disease
M Hafez1, A Abdalla, F el-Shennawy
1Department of Pediatrics, Faculty of Medicine, Mansoura University, Egypt.
Insights
Congenital heart disease (CHD) susceptibility may involve a recessive gene linked to the Human Leukocyte Antigen (HLA) complex. This finding suggests a genetic component influencing CHD development in multiplex families.
Area of Science:
- Human Genetics
- Immunogenetics
- Pediatric Cardiology
Background:
- Congenital heart disease (CHD) is a significant cause of infant mortality and morbidity.
- The genetic basis of isolated CHD in multiplex families remains incompletely understood.
- Human Leukocyte Antigen (HLA) complex plays a crucial role in immune response and has been implicated in various diseases.
Purpose of the Study:
- To investigate the genetic factors contributing to isolated congenital heart diseases (CHD) in multiplex families.
- To explore the potential linkage between CHD susceptibility and the Human Leukocyte Antigen (HLA) complex.
Main Methods:
- Studied 12 multiplex families with isolated CHD, analyzing pedigree, clinical data, and chromosomal analysis.
- Performed Human Leukocyte Antigen (HLA) antigen typing for parents and siblings across A, B, and DR loci.
- Utilized haplotype analysis and Morton's exact test to assess genetic linkage and segregation patterns.
Main Results:
- Identical HLA haplotypes were observed in siblings with different types of CHD.
- Haplotype segregation among affected sibling pairs deviated from Mendelian patterns.
- A statistically significant increase in concordant HLA haplotypes was found among affected siblings.
- Morton's exact test indicated that a recessive susceptibility gene linked to HLA best explains the observed data.
Conclusions:
- The findings suggest a recessive genetic susceptibility locus for isolated CHD, potentially linked to the HLA region.
- HLA haplotype sharing among affected siblings points towards a genetic influence on CHD etiology.
- Further research is warranted to identify specific genes within the HLA complex associated with CHD.
Abstract:
Twelve multiplex families with isolated congenital heart diseases (CHD) were included in the study. In 9 families the types of CHD in the living sibs were concordant and in the other 3 were discordant. All families were subjected to the following: (1) Pedigree construction, (2) clinical examination of the parents, affected and unaffected sibs, (3) investigations of patients, to establish the diagnosis, (4) chromosomal analysis for the patients, (5) HLA antigen typing for the parents, affected and unaffected sibs for 9 antigens at the A locus, 15 at B and 6 at the DR locus. The results can be summarized as: (a) sibs with two different types of CHD showed identical haplotypes; (b) the segregation of haplotypes among disease sibpairs is inconsistent with Mendelian segregation; (c) increased frequency of concordant HLA haplotypes among diseased siblings; (d) Morton's exact test revealed that the data best fit a hypothesis of a recessive susceptibility gene, linked to HLA.