 |
|
- Main page
- News
- RJLabM Credits
- Archive
- Instructions for authors
- Online applications
- Editorial
- About us
-
Links
- Committee on Publication Ethics (COPE)
- International Committee of Medical Journal Editors
- Acta Marisiensis Seria Medica
- Bacteriologia, Virusologia, Parazitologia, Epidemiologia
- Biochemia Medica
- Clinical Chemistry and Laboratory Medicine
- Clinical Chemistry
- Clinica Chimica Acta
- Documenta Haematologica
- Romanian Journal of Morphology and Embryology
- Biostatistics and web search strategies (Romanian)
- How to spot a statistical problem
- Statistical Analyses and Methods in the Published Literature
ISSN online: 2284-5623
ISSN-L: 1841-6624
Rejection rate (2020): 75%
Journal Metrics
Impact Factor 0.5 Five Year Impact Factor 0.5 JCI 0.12
Log in
Concept, Design & Programming
Dr. Adrian Man
Research article Mutational spectrum and genotype-phenotype relationships in a cohort of Romanian hereditary angioedema patients caused by C1 inhibitor deficiency Gabriella Gábos, Dumitru Moldovan, Daniela Dobru, Enikő Mihály, Noémi Bara, Valentin Nădășan, Adina Hutanu, Katalin Csép
Correspondence should be addressed to: Katalin Csép
Abstract: Background: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) caused by SERPING1 mutations is a rare monogenic disorder characterized by a high frequency of de novo mutations, allelic heterogeneity and populational differences. Geno- and phenotype correlation data are limited. Addressing the pathogenic complexity, we proposed to analyze the clinical and genetic characteristics in a set of Romanian patients. Material and Methods: 49 patients from 22 unrelated families with C1-INH-HAE were investigated, by calculating clinical severity score (CSS), C1-INH and C4 level assessment by nephelometric assays, C1-INH function study by functional enzyme-linked immunosorbent assay, and mutation analysis by sequencing and MLPA. Clinical manifestations by missense vs other mutation mechanisms were compared. Results: The mean age at diagnosis and onset was 28.8±14.7 and 15.1±15.2 years, while the diagnostic delay 13.1±10.1 years. CSS ranged from 2 to 9, with a mean of 5.4±1.8. The frequency of missense and nonsense mutations, splice defects, frameshift mutations and large gene rearrangements was 61.22, 6.12, 22.4, 6.12 and 4.08%; in the regulatory sequence no mutation was described. In type II, only missense mutations were noted. Lower levels of C1-INH characterized index cases caused by mechanisms other than missense mutation, with more severe consequences on protein synthesis (p=0.017). 53% of the cases were identified by familial screening. Conclusion: A later onset of disease manifestations and a higher frequency of missense mutations characterize HAE in Romanian patients with SERPING1 mutation. Genetic analysis improves the management of affected families, and may inform about disease severity. Keywords: hereditary angioedema, C1 inhibitor deficiency, SERPING1
Received: 13.2.2019 |
|||||
|
Download full text PDF (643 KB) |
||||
|
Gábos G, Moldovan D, Dobru D, Mihály E, Bara N, Nădășan V, et al. Mutational spectrum and genotype-phenotype relationships in a cohort of Romanian hereditary angioedema patients caused by C1 inhibitor deficiency. Rev Romana Med Lab. 2019;27(3):255-67. DOI:10.2478/rrlm-2019-0029
|
|||||