A Review of the Reported Defects in the Human C1 Esterase Inhibitor Gene Producing Hereditary Angioedema Including Four New Mutations

• Published in: Clinical Immunology Vol. 98; no. 2; pp. 157 - 163
• Main Authors: Bowen, Barbara, Hawk, Jamey Joe, Sibunka, Seth, Hovick, Stephen, Weiler, John M.
• Format: Book Review Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.02.2001; Elsevier
• Subjects: AC1 esterase inhibitors; Allergic diseases; Amino Acid Substitution; angioedema; Angioedema - classification; Angioedema - genetics; Biological and medical sciences; C1 esterase inhibitor; C1 esterase inhibitors; C1 inhibitor; C1INH; complement; Complement C1 Inactivator Proteins - deficiency; Complement C1 Inactivator Proteins - genetics; DNA Mutational Analysis; Exons - genetics; General aspects; hereditary angioedema; Humans; Immunopathology; Introns - genetics; Medical sciences; Mutagenesis, Insertional; Mutation; Mutation, Missense; Point Mutation; RNA Splicing - genetics; serpin; C1 inhibitor; hereditary angioedema; C1INH; complement; C1 esterase inhibitor; serpin; Human; Immunopathology; Allergy; Complement regulatory protein; Complement C1; Serine endopeptidases; Enzyme; Pathogenesis; Clinical form; Classical pathway complement; Peptidases; Angioneurotic edema; Gene; Genetics; Hydrolases; Inhibitor; Mutation
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1006/clim.2000.4947

C1 esterase inhibitor (C1INH) is an important regulatory protein of the classical pathway of complement. Mutations in the gene for this protein cause the autosomal dominant disorder hereditary angioedema (HAE). Approximately 85% of patients with HAE have a Type I defect, characterized by a diminished level of antigenic and functional C1INH. Patients with Type II defects have sufficient protein, but one allele produces dysfunctional protein. We have sequenced the DNA from HAE patients and have discovered four previously unreported mutations. The first mutation is a splice site error at nucleotide 8721, which changes the 3′ acceptor splice site AG to GG at the end of intron 5 at nucleotide 8721–8722. The second mutation is a single base insertion in exon 3 between nucleotides 2467 and 2468. The third mutation is a missense error present in the eighth exon of the C1INH; at nucleotide 16867 (amino acid 470), a T to A mutation transforms a Met to a Lys. The fourth mutation closely resembles the third mutation in that it is a missense error occurring in exon 8 in the distal hinge region; a T16827C substitution changes the Phe at amino acid 457 to Leu. This report compiles a list of 97 distinct defects in the C1INH gene that cause hereditary angioedema.