A Cluster of Mutations within a Short Triplet Repeat in the C1 Inhibitor Gene

Mutations in the C1 inhibitor gene that result in low functional levels of C1 inhibitor protein cause hereditary angioneurotic edema. This disease is characterized by episodic edema leading to considerable morbidity and death. Among 60 unreported kindred with the disease, four patients were discover...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1994-09, Vol.91 (20), p.9622-9625
Main Authors: Bissler, John J., Cicardi, Marco, Donaldson, Virginia H., Gatenby, Paul A., Rosen, Fred S., Sheffer, Albert L., Davis, Alvin E.
Format: Article
Language:English
Subjects:
Alleles
Amino Acid Sequence
Amino acids
Angioedema - blood
Angioedema - genetics
Base Sequence
C1 inhibitor
Codons
Complement C1 Inactivator Proteins - genetics
Deoxyribonucleic acid
Disease
DNA
DNA - blood
DNA - isolation & purification
DNA Primers
DNA Transposable Elements
Edema
Exons
genes
Genetic mutation
Genetics
Humans
Introns
Leukocytes - metabolism
man
Medical research
Molecular Sequence Data
Mutation
Nucleotides
Polymerase Chain Reaction
Repetitive Sequences, Nucleic Acid
Sequence Deletion
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Summary:Mutations in the C1 inhibitor gene that result in low functional levels of C1 inhibitor protein cause hereditary angioneurotic edema. This disease is characterized by episodic edema leading to considerable morbidity and death. Among 60 unreported kindred with the disease, four patients were discovered to have mutations clustered within a 12-bp segment of exon 5 from nucleotide 8449 to nucleotide 8460. This short segment of DNA contains three direct repeats of the triplet CAA and is immediately preceded by a similar adenosine-rich sequence (CAAGAACAC). These triplet repeats make this region susceptible to mutation by a slipped mispairing mechanism. There are two other short triplet repeat elements in the coding region for this gene, but they have not become mutated in any kindred examined. This suggests that the apparent enhanced mutation rate in this region of exon 5 may be influenced by DNA structural characteristics.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.91.20.9622