Identification of a novel and recurrent mutation in the SERPING1 gene in patients with hereditary angioedema

• Published in: Clinical immunology (Orlando, Fla.) Vol. 147; no. 2; pp. 129 - 132
• Main Authors: Firinu, Davide, Colomba, Paolo, Manconi, Paolo Emilio, Barca, Maria P., Fenu, Luisa, Piseddu, Gavino, Zizzo, Carmela, del Giacco, Stefano R., Duro, Giovanni
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2013
• Subjects: Adolescent; Allergy and Immunology; Angioedemas, Hereditary - genetics; C1-inhibitor; Child; Child, Preschool; Complement C1 Inactivator Proteins - genetics; Complement C1 Inhibitor Protein; Female; Founder effect; HAE; Hereditary angioedema; Humans; Italy - epidemiology; Male; Mutation; SERPING1; Young Adult; C1-inhibitor; HRM; Hereditary angioedema; C1-INH; SERPING1; Mutation; Founder effect; HAE; PCR; C1 inhibitor; Serpin peptidase inhibitor clade G, member 1; Polymerase chain reaction; High resolution melting
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2013.03.007

Hereditary angioedema (HAE) due to C1 inhibitor (C1-INH) deficiency is an autosomal dominant disorder caused by mutations in SERPING1 gene. More than 200 different mutations are known, with high genetic heterogeneity and high frequency of private familial mutations. We analyzed for genetic mutations the C1-INH locus in 11 Sardinian families, revealing in seven subjects from four unrelated families the novel nonsense mutation S318X. This mutation, detected with unexpected high frequency, accounts for over a third of the here reported Sardinian families affected by HAE. The recurrence of a pathogenic mutation within the same geographical area is a unique finding, previously unreported in HAE due to C1-INH deficiency. •The novel mutation p.S318X in SERPING1 gene is here reported for in HAE.•This nonsense mutation may be pathogenic and segregated with C1-INH deficiency.•Over a third of Sardinian families affected by HAE type I bear this mutation.•Mutation recurrence in unrelated families is a pretty unique finding in HAE type I.