Mutational spectrum of the SERPING1 gene in patients with hereditary angioedema
https://doi.org/10.29235/1814-6023-2019-16-3-349-356
Abstract
Hereditary angioedema due to the C1-inhibitor deficiency (Type I) or the dysfunction (Type II) is a rare genetic condition characterized by recurrent episodes of edema with an estimated frequency of 1:10 000 and 1:50 000 in the global population without racial or gender differences. HAE Type III is even less common, and unlike Types I and II, it does not appear to be connected with the levels of the C1-inhibitor. For 45 patients (64.44% female; 35.56% male) from 19 unrelated families C1-INH-HAE was confirmed. A series of 19 different mutations in the SERPING1 gene was identified: 17 splicing (37.7%), 15 missense (33.3%), 8 frameshift (17.8%), 3 large del (6.7%), 2 nonsense (4.5%) mutations were found. De novo mutations were detected in 8 patients (17.78%). For 6 patients, the HAE diagnosis was determined at the pre-symptom stage. 9 C1NH mutations had not been previously described. The number of different mutations identified highlights the heterogeneity of the C1 inhibitor deficiency.
Supporting agencies: This work was supported by the Belarusian Republican Foundation for Fundamental Research (Grant no. M18M-004 of May 30, 2018).
About the Authors
I. E. Guryanova
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Belarus
Belarus
Irina E. Guryanova – Researcher
43, Frunzenskaya Str., v. Borovliany, 223053, Minsk Region
K. A. Paliakova
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Belarus
Belarus
Katsiaryna A. Paliakova – Junior researcher
43, Frunzenskaya Str., v. Borovliany, 223053, Minsk Region
M. V. Belevtsev
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Belarus
Belarus
Mikhail V. Belevtsev – Ph. D. (Biol.), Assistant Professor, Head of Research Department
43, Frunzenskaya Str., v. Borovliany, 223053, Minsk Region
O. V. Aleynikova
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Belarus
Belarus
Olga V. Aleynikova – Corresponding Member, D. Sc. (Med.), Professor
43, Frunzenskaya Str., v. Borovliany, 223053, Minsk Region
References
1. Cicardi M., Aberer W., Banerji A., Bas M., Bernstein J. A., Bork K. [et al.]. Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy, 2014, vol. 69, no. 5, pp. 602–616. https://doi.org/10.1111/all.12380
2. Ferkas H., Grumach A., Riedl M. Pathophysiology and clinic of primary angioedema with normal C1 inhibitor. Primary angioedema with normal C1 inhibitor What is new? (October 3–5, 2018). Gazzada Schianno, Italy, 2018, pp. 26–37.
3. Uglova Т. А. Primary immunodeficiency disease: a guide for doctors and patients. Minsk, Nasha Ideya Publ., 2018, 161 p. (in Russian).
4. The Human Gene Mutation Database at the Institute of Medical Genetics in Cardiff. Available at: http://www.hgmd.cf.ac.uk/ac/index.php (accessed 03.10.2018).
5. Agostoni A. Inherited C1 inhibitor deficiency. Complement Inflamm, 1989, vol. 6, pp. 112–118.
6. Ensembl genome browser 95. Available at: http://www.ensembl.org/index.html (accessed 05.04.2019).
7. Venselaar H., Te Beek T. A. H., Kuipers R. K. P., Hekkelman M. L., Vriend G. Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces. BMC Bioinformatics, 2010, vol. 11, no. 1, pp. 1–10. https://doi.org/10.1186/1471-2105-11-548
8. Anastasios E. Germenis. Genotyping C1-INH defciency patients: methods, pitfalls and biases. Allergy, Asthma & Clinical Immunology, 2017, 13 (Suppl. 2). – P. 4. https://doi.org/10.1186/s13223-017-0198-5
Review
For citations:
Guryanova I.E., Paliakova K.A., Belevtsev M.V., Aleynikova O.V. Mutational spectrum of the SERPING1 gene in patients with hereditary angioedema. Proceedings of the National Academy of Sciences of Belarus, Medical series. 2019;16(3):349-356. (In Russ.) https://doi.org/10.29235/1814-6023-2019-16-3-349-356
Views: 889
Email this article 