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Mutational spectrum and phenotypes in Danish families with hereditary angioedema because of C1 inhibitor deficiency.

Anette Bygum 1, * Christina R. Fagerberg 2 D. Ponard 3, 4 Nicole Monnier 5 Joel Lunardi 5 Christian Drouet 4, 6 
* Corresponding author
5 INSERM U836, équipe 4, Muscles et pathologies
GIN - Grenoble Institut des Neurosciences, Laboratoire de biochimie et génétique moléculaire, Centre National de Reference des Angioedemes à Kinines
Abstract : 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.
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Submitted on : Monday, February 21, 2011 - 11:29:36 AM
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Anette Bygum, Christina R. Fagerberg, D. Ponard, Nicole Monnier, Joel Lunardi, et al.. Mutational spectrum and phenotypes in Danish families with hereditary angioedema because of C1 inhibitor deficiency.. Allergy, Wiley, 2011, 66 (1), pp.76-84. ⟨10.1111/j.1398-9995.2010.02456.x⟩. ⟨inserm-00567441⟩



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