%0 Journal Article %T Mutational spectrum and phenotypes in Danish families with hereditary angioedema because of C1 inhibitor deficiency. %+ Department of Dermatology and Allergy Centre %+ Department of Clinical Genetics %+ Laboratoire d'immunohistochimie %+ Centre National de Reference des Angioedemes à Kinines %+ INSERM U836, équipe 4, Muscles et pathologies %+ AGeing and IMagery (AGIM) %A Bygum, Anette %A Fagerberg, Christina, R. %A Ponard, D. %A Monnier, Nicole %A Lunardi, Joel %A Drouet, Christian %Z Kgl. Hofbuntmager Aage Bangs Fond Asthma-Allergi Forbundet, Augustinus Fonden Dansk Dermatologisk Selskabs Forskningsfond Direktør Jacob Madsen & Hustru Olga Madsens Fond Hans & Nora Buchards Fond P.A. Messerschmidt & Hustrus Fond PREHAEAT EU concerted action 2001 and the 2002 PHRC from the French Ministry of Health %< avec comité de lecture %@ 0105-4538 %J Allergy %I Wiley %V 66 %N 1 %P 76-84 %8 2011-01 %D 2011 %R 10.1111/j.1398-9995.2010.02456.x %M 20804470 %K C1 inhibitor deficiency %K hereditary angioedema %K SERPING1 mutation %K severity score %Z Life Sciences [q-bio]/Genetics %Z Life Sciences [q-bio]/Human health and pathologyJournal articles %X BACKGROUND: Hereditary angioedema (HAE), type I and II, is an autosomal dominant disease with deficiency of functional C1 inhibitor protein causing episodic swellings of skin, mucosa and viscera. HAE is a genetically heterogeneous disease with more than 200 different mutations in the SERPING1 gene. A genotype-phenotype relationship does not seem to exist in HAE, although the polymorphism c.-21T>C of exon 2 has been reported to be associated with a more severe phenotype. We aimed to establish the mutational spectrum of C1 inhibitor deficiency in Denmark and investigate the possible disease-aggravating effect of the c.-21T>C polymorphism. METHODS: Hereditary angioedema was diagnosed based on clinical features and C1 inhibitor deficiency. A general severity score ranging from 0 to 10 was developed based on age at disease onset, clinical manifestations and treatment experiences. SERPING1 gene investigation was performed by exon sequencing followed by multiplex ligation-dependent probe amplification genomic rearrangement analysis in all known Danish HAE families. RESULTS: Fifty-nine patients with HAE from 26 families were included in this study. The mean disease severity score was 7.12 [1-10], and the mean C1 inhibitor function was 26% [20-46%]. The sensitivity of the mutational screening was 96%, and 13 new mutations were found in this Danish patient cohort. Nine patients (15%) carried the c.-21T>C polymorphism, but they didn't have a more severe phenotype. CONCLUSION: Thirteen new mutations were identified in the Danish HAE population. No correlation between the c.-21T>C polymorphism, the biochemical values of C1 inhibitor function and the clinical severity score was found. %G English %2 https://inserm.hal.science/inserm-00567441/document %2 https://inserm.hal.science/inserm-00567441/file/Bygum_Mutational_2010.pdf %L inserm-00567441 %U https://inserm.hal.science/inserm-00567441 %~ INSERM %~ EPHE %~ UGA %~ CNRS %~ UNIV-GRENOBLE1 %~ UNIV-PMF_GRENOBLE %~ U836 %~ AGIM %~ PSL %~ TEST-DEV %~ EPHE-PSL %~ TEST3-HALCNRS