Abstract
Mutations that cause low antigenic and functional levels of C1 inhibitor protein result in type 1 hereditary angioneurotic edema. This disease is characterized by episodic edema leading to considerable morbidity and sometimes death. We present here two novel mutations in the reactive center coding region. One mutation is a deletion of an imperfect palindrome encompassing nucleotides 1395–1428 and the other is a direct duplication of nucleotides 1414–1433. These mutations do not depend on improper pairing of direct repeats, but may form as a consequence of a peculiar consensus sequence or an alternative secondary structure.
Similar content being viewed by others
References
Boer JC de, Ripley LS (1984) Demonstration of the production of frameshift and base-substitution mutations by quasipalendromic DNA sequences. Proc Natl Acad Sci USA 81:5528–5531
Cooper DN, Krawczak M (1991) Mechanisms of insertional mutagenesis in human genes causing genetic disease. Hum Genet 87:409–415
Davis AE, Bissler JJ, Aulak KS (1993) Genetic defects in the C1 inhibitor gene. Complement Prof 1:133–150
Donaldson VH, Evans RR (1961) Absence of an enzyme inhibitor in hereditary angioneurotic edema. J Lab Clin Med 58:812
Farabaugh PJ, Schmeissner U, Hofer M, Miller JH (1978) Novel rpoA mutation that interferes with the function of OmpR and EnvZ, positive regulators of the ompF and ompC genes that code for outer-membrane proteins in Escherichia coli K12. J Mol Biol 126:847–853
Glickman BW, Ripley LS (1984) Structural intermediates of deletion mutagenesis: a role for palindrome DNA. Proc Natl Acad Sci USA 81:512–516
Krawczak M, Cooper DN (1991) Gene deletions causing human disease: mechanisms of mutagenesis and the role of the local DNA sequence environment. Hum Genet 86:425–441
Kunkel TA (1985) The mutational specificity of DNA polymerases alpha and gamma during in vitro DNA synthesis. J Biochem 260:12866–12874
Lehrman MA, Schneider WJ, Südhof TC, et al (1985) Mutations in the LDL receptor: Alu—Alu recombination deletes exons encoding transmembrane and cytoplasmic domains. Science 227:140–146
Lehrman MA, Russel DW, Goldstein JL, Brown MS (1986) Exon-Alu recombination deletes 5 kilobases from the low density lipoprotein receptor gene, producing a null phenotype in familial hypercholesterolemia. Proc Natl Acad Sci USA 83:3679–3683
Orita M, Iwahana H, Kanazawa H, Hayashi K, Sekiya T (1991) Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci USA 86:2766–2779
Papanicolaou C, Ripley LS (1992) An in vitro approch to identifying specificity determinants of mutagenesis mediated by DNA misalignments. J Mol Biol 221:805–821
Phear G, Armstrong W, Meuth M (1991) Molecular basis of spontaneous mutations at the APRT locus of hamster cells. J Mol Biol 30:6276–6283
Ripley LS (1990) Frameshift mutations: determinations of specificity. Annu Rev Genet 24:189–213
Sinden RR, Zheng G, Brankamp RG, Allen KN (1991) On the deletion of inverted repeated DNA in Escherichia coli: effects of length, thermal stability, and cruciform formation in vivo. Genetics 129:991–1005
Streisinger G, Okada Y, Emrich J, et al (1966) Frameshift mutations and the genetic code. Cold Spring Harbor Symp Quant Biol 31:77–84
Trinh T, Sinden R (1991) Preferential DNA secondary structure mutagenesis in the lagging strand of replication in E. coli. Nature 352:544–547
Verpy E, Lauerent J, Späth P, Meo T, Tosi M (1991) Clustering f point mutations downstream of the C1 inhibitor reactive site in hereditary angioneurotic edema patients. Complement Inflamm 8:238–239
Weaver DT, De Phamphilis ML (1982) Specific sequences in native DNA that arrest synthesis by DNA polymerase a. J Biol Chem 257:2075–2086
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bissler, J.J., Donaldson, V.H. & Davis, A.E. Contiguous deletion and duplication mutations resulting in type 1 hereditary angioneurotic edema. Hum Genet 93, 265–269 (1994). https://doi.org/10.1007/BF00212020
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00212020