Complex analysis of the national Hereditary angioedema cohort in Slovakia - Identification of 12 novel variants in SERPING1 gene

MARKOCSY, Adam, Katarina HRUBISKOVA, Martin HRUBISKO, Tomáš FREIBERGER, Hana GROMBIŘÍKOVÁ, Lenka DOLESOVA, Ludmila Slivka VAVROVA, Regina Lohajova BEHULOVA, Martina ONDRUSOVA, Peter BANOVCIN, Karolina VORCAKOVA a Milos JESENAK. Complex analysis of the national Hereditary angioedema cohort in Slovakia - Identification of 12 novel variants in SERPING1 gene. WORLD ALLERGY ORGANIZATION JOURNAL. AMSTERDAM: ELSEVIER, 2024, roč. 17, č. 3, s. 1-13. ISSN 1939-4551. Dostupné z: https://dx.doi.org/10.1016/j.waojou.2024.100885.

Základní údaje

• Originální název: Complex analysis of the national Hereditary angioedema cohort in Slovakia - Identification of 12 novel variants in SERPING1 gene
• Autoři: MARKOCSY, Adam, Katarina HRUBISKOVA, Martin HRUBISKO, Tomáš FREIBERGER (203 Česká republika, domácí), Hana GROMBIŘÍKOVÁ (203 Česká republika, domácí), Lenka DOLESOVA, Ludmila Slivka VAVROVA, Regina Lohajova BEHULOVA, Martina ONDRUSOVA, Peter BANOVCIN, Karolina VORCAKOVA a Milos JESENAK.
• Vydání: WORLD ALLERGY ORGANIZATION JOURNAL, AMSTERDAM, ELSEVIER, 2024, 1939-4551.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Článek v odborném periodiku
• Obor: 30102 Immunology
• Stát vydavatele: Nizozemské království
• Utajení: není předmětem státního či obchodního tajemství
• WWW: URL
• Impakt faktor: Impact factor: 5.100 v roce 2022
• Organizační jednotka: Lékařská fakulta
• Doi: http://dx.doi.org/10.1016/j.waojou.2024.100885
• UT WoS: 001217418800001
• Klíčová slova anglicky: Genetic testing; Angioedemas; Hereditary/epidemiology; Hereditary/genetics; Slovakia; Complement C1 inhibitor protein
• Štítky: 14110114, rivok
• Příznaky: Mezinárodní význam, Recenzováno

Anotace

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.