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Pregled bibliografske jedinice broj: 1066205

The Clinical and Genetic Spectrum of 82 Patients With RAG Deficiency Including a c.256_257delAA Founder Variant in Slavic Countries


Sharapova, Svetlana O.; Skomska-Pawliszak, Małgorzata; Rodina, Yulia A.; Wolska-Kuśnierz, Beata; Dabrowska-Leonik, Nel; Mikołuć, Bozena; Pashchenko, Olga E.; Pasic, Srdjan; Freiberger, Tomáš; Milota, Tomáš et al.
The Clinical and Genetic Spectrum of 82 Patients With RAG Deficiency Including a c.256_257delAA Founder Variant in Slavic Countries // Frontiers in Immunology, 11 (2020), 900, 13 doi:10.3389/fimmu.2020.00900 (međunarodna recenzija, članak, znanstveni)


CROSBI ID: 1066205 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
The Clinical and Genetic Spectrum of 82 Patients With RAG Deficiency Including a c.256_257delAA Founder Variant in Slavic Countries

Autori
Sharapova, Svetlana O. ; Skomska-Pawliszak, Małgorzata ; Rodina, Yulia A. ; Wolska-Kuśnierz, Beata ; Dabrowska-Leonik, Nel ; Mikołuć, Bozena ; Pashchenko, Olga E. ; Pasic, Srdjan ; Freiberger, Tomáš ; Milota, Tomáš ; Formánková, Renata ; Szaflarska, Anna ; Siedlar, Maciej ; Avčin, Tadej ; Markelj, Gašper ; Ciznar, Peter ; Kalwak, Krzysztof ; Kołtan, Sylwia ; Jackowska, Teresa ; Drabko, Katarzyna ; Gagro, Alenka ; Pac, Małgorzata ; Naumova, Elissaveta ; Kandilarova, Snezhina ; Babol-Pokora, Katarzyna ; Varabyou, Dzmitry S. ; Barendregt, Barbara H. ; Raykina, Elena V. ; Varlamova, Tatiana V. ; Pavlova, Anna V. ; Grombirikova, Hana ; Debeljak, Maruša ; Mersiyanova, Irina V. ; Bondarenko, Anastasiia V. ; Chernyshova, Liudmyla I. ; Kostyuchenko, Larysa V. ; Guseva, Marina N. ; Rascon, Jelena ; Muleviciene, Audrone ; Preiksaitiene, Egle ; Geier, Christoph B. ; Leiss-Piller, Alexander ; Yamazaki, Yasuhiro ; Kawai, Tomoki ; Walter, Jolan E. ; Kondratenko, Irina V. ; Šedivá, Anna ; van der Burg, Mirjam ; Kuzmenko, Natalia B. ; Notarangelo, Luigi D. ; Bernatowska, Ewa ; Aleinikova, Olga V.

Izvornik
Frontiers in Immunology (1664-3224) 11 (2020); 900, 13

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
RAG1, RAG2, primary immunodeficiency, geographic distribution, incidence, Slavic children

Sažetak
Background: Variants in recombination-activating genes (RAG) are common genetic causes of autosomal recessive forms of combined immunodeficiencies (CID) ranging from severe combined immunodeficiency (SCID), Omenn syndrome (OS), leaky SCID, and CID with granulomas and/or autoimmunity (CID-G/AI), and even milder presentation with antibody deficiency. Objective: We aim to estimate the incidence, clinical presentation, genetic variability, and treatment outcome with geographic distribution of patients with the RAG defects in populations inhabiting South, West, and East Slavic countries. Methods: Demographic, clinical, and laboratory data were collected from RAG-deficient patients of Slavic origin via chart review, retrospectively. Recombinase activity was determined in vitro by flow cytometry-based assay. Results: Based on the clinical and immunologic phenotype, our cohort of 82 patients from 68 families represented a wide spectrum of RAG deficiencies, including SCID (n = 20), OS (n = 37), and LS/CID (n = 25) phenotypes. Sixty-seven (81.7%) patients carried RAG1 and 15 patients (18.3%) carried RAG2 biallelic variants. We estimate that the minimal annual incidence of RAG deficiency in Slavic countries varies between 1 in 180, 000 and 1 in 300, 000 live births, and it may vary secondary to health care disparities in these regions. In our cohort, 70% (n = 47) of patients with RAG1 variants carried p.K86Vfs*33 (c.256_257delAA) allele, either in homozygous (n = 18, 27%) or in compound heterozygous (n = 29, 43%) form. The majority (77%) of patients with homozygous RAG1 p.K86Vfs*33 variant originated from Vistula watershed area in Central and Eastern Poland, and compound heterozygote cases were distributed among all Slavic countries except Bulgaria. Clinical and immunological presentation of homozygous RAG1 p.K86Vfs*33 cases was highly diverse (SCID, OS, and AS/CID) suggestive of strong influence of additional genetic and/or epigenetic factors in shaping the final phenotype. Conclusion: We propose that RAG1 p.K86Vfs*33 is a founder variant originating from the Vistula watershed region in Poland, which may explain a high proportion of homozygous cases from Central and Eastern Poland and the presence of the variant in all Slavs. Our studies in this cohort of RAG1 founder variants confirm that clinical and immunological phenotypes only partially depend on the underlying genetic defect. As access to HSCT is improving among RAG-deficient patients in Eastern Europe, we anticipate improvements in survival.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti



POVEZANOST RADA


Projekti:
072-1080229-0337 - Modulacija funkcije ljudskih regulacijskih T-limfocita (Gagro, Alenka, MZOS ) ( POIROT)

Ustanove:
Klinika za dječje bolesti Medicinskog fakulteta,
Medicinski fakultet, Zagreb,
Medicinski fakultet, Osijek,
Sveučilište u Zagrebu,
Sveučilište J. J. Strossmayera u Osijeku

Profili:

Avatar Url Alenka Gagro (autor)

Citiraj ovu publikaciju

Sharapova, Svetlana O.; Skomska-Pawliszak, Małgorzata; Rodina, Yulia A.; Wolska-Kuśnierz, Beata; Dabrowska-Leonik, Nel; Mikołuć, Bozena; Pashchenko, Olga E.; Pasic, Srdjan; Freiberger, Tomáš; Milota, Tomáš et al.
The Clinical and Genetic Spectrum of 82 Patients With RAG Deficiency Including a c.256_257delAA Founder Variant in Slavic Countries // Frontiers in Immunology, 11 (2020), 900, 13 doi:10.3389/fimmu.2020.00900 (međunarodna recenzija, članak, znanstveni)
Sharapova, S., Skomska-Pawliszak, M., Rodina, Y., Wolska-Kuśnierz, B., Dabrowska-Leonik, N., Mikołuć, B., Pashchenko, O., Pasic, S., Freiberger, T. & Milota, T. (2020) The Clinical and Genetic Spectrum of 82 Patients With RAG Deficiency Including a c.256_257delAA Founder Variant in Slavic Countries. Frontiers in Immunology, 11, 900, 13 doi:10.3389/fimmu.2020.00900.
@article{article, year = {2020}, pages = {13}, DOI = {10.3389/fimmu.2020.00900}, chapter = {900}, keywords = {RAG1, RAG2, primary immunodeficiency, geographic distribution, incidence, Slavic children}, journal = {Frontiers in Immunology}, doi = {10.3389/fimmu.2020.00900}, volume = {11}, issn = {1664-3224}, title = {The Clinical and Genetic Spectrum of 82 Patients With RAG Deficiency Including a c.256\_257delAA Founder Variant in Slavic Countries}, keyword = {RAG1, RAG2, primary immunodeficiency, geographic distribution, incidence, Slavic children}, chapternumber = {900} }
@article{article, year = {2020}, pages = {13}, DOI = {10.3389/fimmu.2020.00900}, chapter = {900}, keywords = {RAG1, RAG2, primary immunodeficiency, geographic distribution, incidence, Slavic children}, journal = {Frontiers in Immunology}, doi = {10.3389/fimmu.2020.00900}, volume = {11}, issn = {1664-3224}, title = {The Clinical and Genetic Spectrum of 82 Patients With RAG Deficiency Including a c.256\_257delAA Founder Variant in Slavic Countries}, keyword = {RAG1, RAG2, primary immunodeficiency, geographic distribution, incidence, Slavic children}, chapternumber = {900} }

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