BACKGROUND: Hereditary angioedema (HAE) is a rare autosomal dominant genetic disease characterised by acute episodes of non-pruritic skin and submucosal swelling caused by increase in vascular permeability. OBJECTIVE: Here we present the first complex analysis of the National HAE Slovakian cohort with the detection of 12 previously un-published genetic variants in SERPING1 gene. METHODS: In patients diagnosed with hereditary angioedema caused by deficiency or dysfunction of C1 inhibitor (C1-INH-HAE) based on clinical manifestation and complement measurements, SERPING1 gene was tested by DNA sequencing (Sanger sequencing/massive parallel sequencing) and/or multiplex ligation-dependent probe amplification for detection of large rearrangements. RESULTS: The Slovakian national cohort consisted of 132 living patients with confirmed HAE. We identified 51 index cases (32 families, 19 sporadic patients/112 adults, 20 children). One hundred seventeen patients had HAE caused by deficiency of C1 inhibitor (C1-INH-HAE-1) and 15 patients had HAE caused by dysfunction of C1 inhibitor (C1-INH-HAE-2). The prevalence of HAE in Slovakia has recently been calculated to 1:41 280 which is higher than average calculated prevalence. The estimated incidence was 1:1360 000. Molecular-genetic testing of the SERPING1 gene found 22 unique causal variants in 26 index cases, including 12 previously undescribed and unreported. CONCLUSION: The first complex report about epidemiology and genetics of the Slovakian national HAE cohort expands the knowledge of the C1-INH-HAE genetics. Twelve novel causal variants were present in the half of the index cases. A higher percentage of inframe variants comparing to other studies was observed. Heterozygous deletion of exon 3 found in a large C1-INH-HAE-1 family probably causes the dysregulation of the splicing isoforms balance and leads to the decrease of full-length C1-INH level.

Centre for Cardiovascular Surgery and Transplantation Brno Czech Republic

Centre for Hereditary Angioedema 5th Clinic of Internal Medicine Faculty of Medicine Comenius University in Bratislava University Hospital Bratislava Bratislava Slovakia

Clinic of Dermatovenerology Jessenius Faculty of Medicine Comenius University in Bratislava University Hospital in Martin Slovakia

Department of Clinical Immunology and Allergology Jessenius Faculty of Medicine Comenius University in Bratislava University Hospital in Martin Slovakia

Department of Clinical Immunology and Allergology St Elisabeth Cancer Institute in Bratislava Slovakia

Department of Medical Genetics St Elisabeth Cancer Institute in Bratislava Slovakia

Faculty of Medicine Masaryk University Brno Czech Republic

Faculty of Public Health Slovak Medical University Bratislava Slovakia

National Centre for Hereditary Angioedema Clinic of Children and Adolescents Clinics of Pulmonology and Phthisiology Jessenius Faculty of Medicine Comenius University in Bratislava University Hospital in Martin Slovakia

Pharm In Ltd Bratislava Slovakia

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