Haplotypes of the steroid 21-hydroxylase gene region encoding mild steroid 21-hydroxylase deficiency.
- 1 October 1991
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 88 (19), 8352-8356
- https://doi.org/10.1073/pnas.88.19.8352
Abstract
Haplotypes of the complement 4 (C4) and steroid 21-hydroxylase [21-OHase; steroid hydrogen-donor: oxygen oxidoreductase (21-hydroxylating), EC 1.14.99.10] repeated gene complex were studied in nine families with at least one member affected with a mild form of 21-OHase deficiency. DNA probes from different parts of the repeated C4/21-OHase unit were used to follow the segregation of hybridization patterns in the families. Ten structurally distinct haplotypes of the C4/21-OHase gene region were identified, and the encoded phenotype was assigned to 34 of the 36 C4/21-OHase haplotypes. Four structurally different haplotypes with three C4/21-OHase repeat units were found. Eight of the nine haplotypes found with triplications of the C4/21-OHase repeat unit encoded the mild form of 21-OHase deficiency, whereas one particular triplicated haplotype encoded a severe form of the disease. In one case the mild form of 21-OHase deficiency was encoded by a haplotype with a single C4/21-OHase repeat unit. Mild 21-OHase deficiency was predicted in a patient by the presence of a triplicated haplotype. The finding of deranged 21-OHase genes on all triplicated C4/21-OHase haplotypes indicate that most of these common haplotypes carry mutated 21-OHase genes, and thus may cause functional polymorphism of general importance in the population.Keywords
This publication has 22 references indexed in Scilit:
- TaqI HLA-B and -DRB RFLP analysis can predict disease in siblings of affected children with 21-hydroxylase deficiencyHuman Genetics, 1990
- THE MOLECULAR GENETICS OF 21-HYDROXYLASE DEFICIENCYAnnual Review of Genetics, 1989
- Direct observation of the gene organization of the complement C4 and 21-hydroxylase loci by pulsed field gel electrophoresis.The Journal of Experimental Medicine, 1989
- Extensive deletions and insertions in different MHC supratypes detected by pusled field gel electrophoresis.The Journal of Experimental Medicine, 1988
- Restriction fragment length polymorphisms of the complement component C4 loci on chromosome 6: studies with emphasis on the determination of gene numberAnnals of Human Genetics, 1988
- Congenital Adrenal HyperplasiaThe New England Journal of Medicine, 1987
- Associations between restriction fragment length polymorphisms detected with a probe for human 21-hydroxylase (21-OH) and two clinical forms of 21-OH deficiencyHuman Genetics, 1986
- Polymorphism of the human complement C4 and steroid 21-hydroxylase genes. Restriction fragment length polymorphisms revealing structural deletions, homoduplications, and size variants.JCI Insight, 1986
- Molecular Genetics of the Fourth Component of Human Complement and Steroid 21‐HydroxylaseImmunological Reviews, 1985
- The structural basis of the multiple forms of human complement component C4Cell, 1984