Restriction fragment length polymorphism analysis of the C1-inhibitor gene in hereditary C1-inhibitor deficiency.

Four out of 12 kindreds with Type I hereditary angio-oedema (HAE) were shown to have unique disease-related restriction fragment length polymorphism (RFLPs) in one allele of the C1-inhibitor gene. These RFLPs were used to localise the gene mutations responsible for them in each family. The four mutations affected exon 4, exon 6, exon 7 and exon 8, respectively. Mutations in exon 6 and exon 8 have not been described previously in Type I HAE. The other two mutations which comprised an exon 4 deletion and an exon 7 deletion have already been documented by other investigators. In each family the mutation was seen to cosegregate with the disease. Detection of a disease-related RFLP in 30% of the Type I HAE kindred tested is higher than other published studies, and reflects the larger number of restriction enzymes employed. These results suggest that Type I HAE is likely to be associated with a multiplicity of gene mutations as is seen in other genetic diseases. A new C1-inhibitor gene-related RFLP in the normal population was also characterised. This may be useful as an indirect marker of the mutant C1-inhibitor allele in certain families with Type I HAE.