Restriction fragment length polymorphism of the C1 inhibitor gene in hereditary angioneurotic edema.
Open Access
- 1 December 1987
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 80 (6), 1640-1643
- https://doi.org/10.1172/jci113252
Abstract
Hereditary angioneurotic edema (HANE) results from the deficiency of the inhibitor of the first component of human complement (C1-INH). It is inherited as an autosomal dominant trait. Heterogeneity of this defect has been shown at the protein and mRNA level. Southern blot analysis of genomic DNA was performed after digestion with six different restriction endonucleases in 24 families affected with type 1 HANE (low antigenic and functional C1-INH levels) and five with type 2 (low functional C1-INH levels and normal or elevated levels of dysmorphic C1-INH). Blots were hybridized with a C1-INH cDNA probe of 1,227 bp. With one enzyme (Pst I), two different patterns of restriction fragment length polymorphism (RFLP) were detected. One was present in one kindred with type 1 HANE and the other appeared the same in one type 1 and in one type 2 family, thus indicating that each RFLP resulted from a different mutation. Analysis of a total of 34 members of these three families suggested that the polymorphisms are tightly linked to the mutation responsible for the disease. Using a 170-bp probe we showed that the three different mutations leading to these polymorphisms are located in the same region of the C1-INH gene. These data suggest that different mutations in the same region of the C1-INH gene are responsible for C1-INH deficiency in these families. Most of these mutations are probably point mutations or other "minor" defects and do not appear to be due to major deletions or rearrangements.This publication has 15 references indexed in Scilit:
- Immunoregulatory disorders associated with hereditary angioedema: II. Serologic and cellular abnormalitiesJournal of Allergy and Clinical Immunology, 1986
- Immunoregulatory disorders associated with hereditary angioedema: I. Clinical manifestations of autoimmune diseaseJournal of Allergy and Clinical Immunology, 1986
- Human inhibitor of the first component of complement, C1: characterization of cDNA clones and localization of the gene to chromosome 11.Proceedings of the National Academy of Sciences of the United States of America, 1986
- DNA Polymorphism of the C4 GenesThe New England Journal of Medicine, 1984
- C1 INH Concentrate in the Therapy of Hereditary AngioedemaAllergy, 1983
- Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate.Proceedings of the National Academy of Sciences of the United States of America, 1979
- Response of Variant Hereditary Angioedema Phenotypes to Danazol TherapyJCI Insight, 1979
- Treatment of Hereditary Angioedema with DanazolThe New England Journal of Medicine, 1976
- Genetically determined heterogeneity of the C1 esterase inhibitor in patients with hereditary angioneurotic edemaJCI Insight, 1971
- A biochemical abnormality in hereditary angioneurotic edema: Absence of serum inhibitor of C′1-esteraseAmerican Journal Of Medicine, 1963