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Title:Hereditary angioedema due to C1-inhibitor deficiency in Macedonia : clinical characteristics, novel SERPING1 mutations, and genetic factors modifying the clinical phenotype
Authors:Grivčeva-Panovska, Vesna (Author)
Košnik, Mitja (Author)
Korošec, Peter (Author)
Andrejević, Slađana (Author)
Karadža-Lapić, Ljerka (Author)
Rijavec, Matija (Author)
Language:English
Tipology:1.01 - Original Scientific Article
Organisation:Logo UKPBAG - University Clinic of Respiratory and Allergic Diseases Golnik
Abstract:Objective: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disease, characterized by swellings. We aimed to characterize on a clinical and molecular basis C1-INH-HAE patients in the Republic of Macedonia. Results: All 15 patients from six unrelated families were diagnosed with C1-INHHAE type I, with a mean age of symptom onset of 11 years and an average delay of diagnosis of 7 years. Patients reported on average 31 angioedema attacks/year, with a median clinical severity score (CSS) of 7. We identified three known mutations, and two mutations (c.813_818delCAACAA and c.1488T>G) were reported for the first time. To address the genotype-phenotype association, a pooled analysis including 78 C1-INH-HAE south-eastern European patients was performed, with additional analysis of F12-46C/T and KLKB1- 428G/A polymorphisms. We demonstrated that patients with nonsense and frameshift mutations, large deletions/insertions, splicing defects, and mutations at Arg444 exhibited an increased CSS compared with missense mutations, excluding mutations at Arg444. In addition, the CC F12-46C/T polymorphism was suggestive of earlier disease onset. Discussion: Genetic analysis helped identify the molecular basis of C1-INH-HAE given that causative mutations in SERPING1 were detected in all patients, including an infant before the appearance of clinical symptoms. We identified two novel mutations and further corroborated the genotype-phenotype relationship, wherein mutations with a clear effect on C1-INH function predispose patients to a more severe disease phenotype and CC F12-46C/T predisposes patients to earlier disease onset.
Keywords:hereditary angioedemas -- genetics -- Macedonia, C1 inhibitor, SERPING1 gene, C1 inhibitor, SERPING1 gene
Year of publishing:2018
Publisher:Taylor & Francis
Source:Velika Britanija
COBISS_ID:2048261745 Link is opened in a new window
UDC:616-097
ISSN on article:1365-2060
OceCobissID:521184793 Link is opened in a new window
DOI:10.1080/07853890.2018.1449959 Link is opened in a new window
Note:Soavtorji: Mitja Košnik, Peter Korošec, Slađana Andrejević, Ljerka Karadža-Lapić, Matija Rijavec; Nasl. z nasl. zaslona; Opis vira z dne 19. 3. 2018;
Views:743
Downloads:139
Files:URL URL - Source URL, visit https://www.tandfonline.com/doi/abs/10.1080/07853890.2018.1449959?journalCode=iann20
 
Journal:Ann. med.
Taylor & Francis Ltd
 
Metadata:XML RDF-CHPDL DC-XML DC-RDF
Rights:2018 Informa UK Limited
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