Complex analysis of the national Hereditary angioedema cohort in Slovakia – Identification of 12 novel variants in SERPING1 gene
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 wi...
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Elsevier
2024-03-01
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| Series: | World Allergy Organization Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1939455124000164 |
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| author | Adam Markocsy, MD Katarina Hrubiskova, MD Martin Hrubisko, MD, PhD Tomas Freiberger, MD, PhD Hana Grombirikova, MSc Lenka Dolesova, MSc, PhD Ludmila Slivka Vavrova, MSc, PhD Regina Lohajova Behulova, MSc, PhD Martina Ondrusova, MSc, PhD, MPH Peter Banovcin, MD, PhD Karolina Vorcakova, MD, PhD Milos Jesenak, MD, MSc, PhD, MBA, MHA, FAAAAI |
| author_facet | Adam Markocsy, MD Katarina Hrubiskova, MD Martin Hrubisko, MD, PhD Tomas Freiberger, MD, PhD Hana Grombirikova, MSc Lenka Dolesova, MSc, PhD Ludmila Slivka Vavrova, MSc, PhD Regina Lohajova Behulova, MSc, PhD Martina Ondrusova, MSc, PhD, MPH Peter Banovcin, MD, PhD Karolina Vorcakova, MD, PhD Milos Jesenak, MD, MSc, PhD, MBA, MHA, FAAAAI |
| author_sort | Adam Markocsy, MD |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T21:43:02Z |
| format | Article |
| id | doaj.art-d13cecf11d30490faf8a2fcf30cc907f |
| institution | Directory Open Access Journal |
| issn | 1939-4551 |
| language | English |
| last_indexed | 2024-04-24T21:43:02Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
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| series | World Allergy Organization Journal |
| spelling | doaj.art-d13cecf11d30490faf8a2fcf30cc907f2024-03-21T05:36:14ZengElsevierWorld Allergy Organization Journal1939-45512024-03-01173100885Complex analysis of the national Hereditary angioedema cohort in Slovakia – Identification of 12 novel variants in SERPING1 geneAdam Markocsy, MD0Katarina Hrubiskova, MD1Martin Hrubisko, MD, PhD2Tomas Freiberger, MD, PhD3Hana Grombirikova, MSc4Lenka Dolesova, MSc, PhD5Ludmila Slivka Vavrova, MSc, PhD6Regina Lohajova Behulova, MSc, PhD7Martina Ondrusova, MSc, PhD, MPH8Peter Banovcin, MD, PhD9Karolina Vorcakova, MD, PhD10Milos Jesenak, MD, MSc, PhD, MBA, MHA, FAAAAI11National 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, SlovakiaCentre for Hereditary Angioedema, 5th Clinic of Internal Medicine, Faculty of Medicine, Comenius University in Bratislava, University Hospital Bratislava, Bratislava, SlovakiaDepartment of Clinical Immunology and Allergology, St. Elisabeth Cancer Institute in Bratislava, SlovakiaCentre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic; Faculty of Medicine, Masaryk University, Brno, Czech RepublicCentre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic; Faculty of Medicine, Masaryk University, Brno, Czech RepublicDepartment of Medical Genetics, St. Elisabeth Cancer Institute in Bratislava, SlovakiaDepartment of Medical Genetics, St. Elisabeth Cancer Institute in Bratislava, SlovakiaDepartment of Medical Genetics, St. Elisabeth Cancer Institute in Bratislava, SlovakiaPharm-In, Ltd., Bratislava, Slovakia; Faculty of Public Health, Slovak Medical University, Bratislava, SlovakiaNational 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, SlovakiaClinic of Dermatovenerology, Jessenius Faculty of Medicine, Comenius University in Bratislava, University Hospital in Martin, Slovakia; Corresponding author.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; Department of Clinical Immunology and Allergology, Jessenius Faculty of Medicine, Comenius University in Bratislava, University Hospital in Martin, Slovakia; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S1939455124000164Genetic testingAngioedemasHereditary/epidemiologyHereditary/geneticsSlovakiaComplement C1 inhibitor protein |
| spellingShingle | Adam Markocsy, MD Katarina Hrubiskova, MD Martin Hrubisko, MD, PhD Tomas Freiberger, MD, PhD Hana Grombirikova, MSc Lenka Dolesova, MSc, PhD Ludmila Slivka Vavrova, MSc, PhD Regina Lohajova Behulova, MSc, PhD Martina Ondrusova, MSc, PhD, MPH Peter Banovcin, MD, PhD Karolina Vorcakova, MD, PhD Milos Jesenak, MD, MSc, PhD, MBA, MHA, FAAAAI Complex analysis of the national Hereditary angioedema cohort in Slovakia – Identification of 12 novel variants in SERPING1 gene World Allergy Organization Journal Genetic testing Angioedemas Hereditary/epidemiology Hereditary/genetics Slovakia Complement C1 inhibitor protein |
| title | Complex analysis of the national Hereditary angioedema cohort in Slovakia – Identification of 12 novel variants in SERPING1 gene |
| title_full | Complex analysis of the national Hereditary angioedema cohort in Slovakia – Identification of 12 novel variants in SERPING1 gene |
| title_fullStr | Complex analysis of the national Hereditary angioedema cohort in Slovakia – Identification of 12 novel variants in SERPING1 gene |
| title_full_unstemmed | Complex analysis of the national Hereditary angioedema cohort in Slovakia – Identification of 12 novel variants in SERPING1 gene |
| title_short | Complex analysis of the national Hereditary angioedema cohort in Slovakia – Identification of 12 novel variants in SERPING1 gene |
| title_sort | complex analysis of the national hereditary angioedema cohort in slovakia identification of 12 novel variants in serping1 gene |
| topic | Genetic testing Angioedemas Hereditary/epidemiology Hereditary/genetics Slovakia Complement C1 inhibitor protein |
| url | http://www.sciencedirect.com/science/article/pii/S1939455124000164 |
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