title: Identification and characterization of a novel splice site mutation in the SERPING1 gene in a family with hereditary angioedema.
abstract: Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH) is a rare autosomal-dominant disease caused by mutations in SERPING1 gene. The main clinical feature of C1INH deficiency is the spontaneous edema of the subcutaneous and submucosal layers. More than 280 different mutations scattering the entire SERPING1 gene have been reported. We identified and characterized a new mutation in SERPING1 gene in a Spanish family with hereditary angioedema. The mutation (c.685 + 2 T > A) disrupts the donor splice site of intron 4 leading to the loss of exon 4 in mutant mRNA. We demonstrated that mutant mRNA is mostly degraded, probably by the surveillance pathway no-go mRNA decay. Bioinformatic analysis showed that the mutant protein, if produced, would be non-functional since the protein lacks a stretch of 45 amino acids affecting the functional RCL loop. Finally, we found a reduction of the wild-type mRNA expression in c.685 + 2 T > A carriers.
authors.affiliation: Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Barcelona, Spain; Clinical and Molecular Genetic Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
authors.forename: Roger
authors.initials: R
authors.lastname: Colobran
authors.affiliation: Research Unit in Translational Bioinformatics in Neurosciences, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Lois
authors.affiliation: Research Unit in Translational Bioinformatics in Neurosciences, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Catalonia, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: de la Cruz
authors.affiliation: Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Barcelona, Spain. Electronic address: rpujol@vhebron.net.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pujol-Borrell
authors.affiliation: Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Hernández-González
authors.affiliation: Allergy Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Guilarte
mesh_terms: D000328:Adult; D054179:Angioedemas, Hereditary / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D003174:Complement C1 Inactivator Proteins / Q000737:chemistry / Q000235:genetics*; D050718:Complement C1 Inhibitor Protein; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D009690:Nucleic Acid Conformation; D010375:Pedigree; D011487:Protein Conformation; D022821:RNA Splice Sites; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D017422:Sequence Analysis, DNA; D013030:Spain
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D022821:RNA Splice Sites; D012333:RNA, Messenger; C469952:SERPING1 protein, human
keywords: C1-inhibitor;; Hereditary angioedema;; Immunodeficiency;; Mutation;; SERPING1;; Splicing