A novel mutation in the coagulation factor 12 gene in subjects with hereditary angioedema and normal C1-inhibitor

• Published in: Clinical immunology (Orlando, Fla.) Vol. 141; no. 1; pp. 31 - 35
• Main Authors: Bork, Konrad, Wulff, Karin, Meinke, Peter, Wagner, Nicola, Hardt, Jochen, Witzke, Günther
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.10.2011; Elsevier
• Subjects: Adult; Allergic diseases; Allergy and Immunology; Angioedema; Angioedemas, Hereditary - blood; Angioedemas, Hereditary - genetics; Angioedemas, Hereditary - immunology; Base pairs; Biological and medical sciences; Coagulation factor XII; Coagulation factors; Codons; Complement C1 Inhibitor Protein - genetics; Complement C1 Inhibitor Protein - metabolism; DNA Mutational Analysis; Exons; Factor 12 gene mutation; Factor XII - chemistry; Factor XII - genetics; Factor XII Deficiency - blood; Factor XII Deficiency - genetics; Factor XII Deficiency - immunology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene deletion; Hereditary angioedema type III; Hereditary angioedema with normal C1-inhibitor; Humans; Immunopathology; Introns; Male; Medical sciences; Missense mutation; Mutation; Mutation, Missense; Pain; Pedigree; Point mutation; Sequence Deletion; Skin; Skin allergic diseases. Stinging insect allergies; Turkey - ethnology; Turkey; aPTT; F12; Angioedema; Hereditary angioedema with normal C1-inhibitor; Hereditary angioedema type III; HAE-C1-INH; FXIIa; HAE; bp; HAE-FXII; FXII; DNA; C1-INH; Factor 12 gene mutation; PCR; Coagulation factor XII; Activated coagulation factor XII; C1-esterase inhibitor; Activated partial thromboplastin time; Deoxyribonucleic acid; Hereditary angioedema with a mutation in the factor 12 gene; HAE due to C1-INH deficiency; Base pair(s); Coagulation factor 12 gene; Polymerase chain reaction; Hereditary angioedema; Human; Allergy; Immunopathology; Skin disease; Complement C1; with normal C1-inhibitor; Hereditary; Factor XII; Angioneurotic edema; Immunology; Gene; Genetics; Inhibitor; Mutation; type III; Coagulation factor
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2011.07.002

In hereditary angioedema with normal C1-inhibitor two different missense mutations of codon p.Thr328* in the coagulation factor 12 gene have been reported in some families. In this study a novel factor 12 gene mutation, the deletion of 72 base pairs (bp) (c.971_1018+24del72*), was identified in a family of Turkish origin, in two sisters with recurrent skin swellings and abdominal pain attacks and in their symptom-free father. This deletion caused a loss of 48bp of exon 9 (coding amino acids 324* to 340*) in addition to 24bp of intron 9, including the authentic donor splice site of exon 9. The large deletion of 72bp was located in the same F12 gene region as the missense mutations p.Thr328Lys* and p.Thr328Arg* reported previously. Our findings confirm the association between F12 gene mutations modifying the proline-rich region of the FXII protein and hereditary angioedema with normal C1-inhibitor. ► Patients with HAE and normal C1-INH are examined for mutations in the F12 gene. ► A novel mutation, a large deletion, was identified in three members of one family. ► The mutation is located in the region coding the proline-rich FXII protein region. ► Our data confirm an association between HAE with normal C1-INH and F12 mutations.