SHARAPOVA, S. O., M. SKOMSKA-PAWLISZAK, Y. A. RODINA, B. WOLSKA-KUSNIERZ, N. DABROWSKA-LEONIK, B. MIKOLUC, O. E. PASHCHENKO, S. PASIC, Tomáš FREIBERGER, T. MILOTA, R. FORMANKOVA, A. SZAFLARSKA, M. SIEDLAR, T. AVCIN, G. MARKELJ, P. CIZNAR, K. KALWAK, S. KOTTAN, T. JACKOWSKA, K. DRABKO, A. GAGRO, M. PAC, E. NAUMOVA, S. KANDILAROVA, K. BABOL-POKORA, D. S. VARABYOU, B. H. BARENDREGT, E. V. RAYKINA, T. V. VARLAMOVA, A. V. PAVLOVA, Hana GROMBIŘÍKOVÁ, M. DEBELJAK, I. V. MERSIYANOVA, A. V BONDARENKO, L. I. CHERNYSHOVA, L. V. KOSTYUCHENKO, M. N. GUSEVA, J. RASCON, A. MULEVICIENE, E. PREIKSAITIENE, C. B. GEIER, A. LEISS-PILLER, Y. YAMAZAKI, T. KAWAI, J. E. WALTER, I.V. KONDRATENKO, A. SEDIVA, M. VAN DER BURG, N. B. KUZMENKO, L. D. NOTARANGELO, E. BERNATOWSKA a O. V. ALEINIKOVA. The Clinical and Genetic Spectrum of 82 Patients WithRAGDeficiency Including a c.256_257delAA Founder Variant in Slavic Countries. Frontiers in Immunology. LAUSANNE: FRONTIERS MEDIA SA, roč. 11, June 2020, s. 1-13. ISSN 1664-3224. doi:10.3389/fimmu.2020.00900. 2020.
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Základní údaje
Originální název The Clinical and Genetic Spectrum of 82 Patients WithRAGDeficiency Including a c.256_257delAA Founder Variant in Slavic Countries
Autoři SHARAPOVA, S. O. (112 Bělorusko, garant), M. SKOMSKA-PAWLISZAK (616 Polsko), Y. A. RODINA (643 Rusko), B. WOLSKA-KUSNIERZ (616 Polsko), N. DABROWSKA-LEONIK (616 Polsko), B. MIKOLUC (616 Polsko), O. E. PASHCHENKO (643 Rusko), S. PASIC (688 Srbsko), Tomáš FREIBERGER (203 Česká republika, domácí), T. MILOTA (203 Česká republika), R. FORMANKOVA (203 Česká republika), A. SZAFLARSKA (616 Polsko), M. SIEDLAR (705 Slovinsko), T. AVCIN (705 Slovinsko), G. MARKELJ (705 Slovinsko), P. CIZNAR (703 Slovensko), K. KALWAK (616 Polsko), S. KOTTAN (616 Polsko), T. JACKOWSKA (616 Polsko), K. DRABKO (616 Polsko), A. GAGRO (191 Chorvatsko), M. PAC (616 Polsko), E. NAUMOVA (100 Bulharsko), S. KANDILAROVA (100 Bulharsko), K. BABOL-POKORA (616 Polsko), D. S. VARABYOU (112 Bělorusko), B. H. BARENDREGT (528 Nizozemské království), E. V. RAYKINA (643 Rusko), T. V. VARLAMOVA (643 Rusko), A. V. PAVLOVA (643 Rusko), Hana GROMBIŘÍKOVÁ (203 Česká republika, domácí), M. DEBELJAK (703 Slovensko), I. V. MERSIYANOVA (643 Rusko), A. V BONDARENKO (804 Ukrajina), L. I. CHERNYSHOVA (804 Ukrajina), L. V. KOSTYUCHENKO (804 Ukrajina), M. N. GUSEVA (643 Rusko), J. RASCON (440 Litva), A. MULEVICIENE (440 Litva), E. PREIKSAITIENE (440 Litva), C. B. GEIER (40 Rakousko), A. LEISS-PILLER (40 Rakousko), Y. YAMAZAKI (840 Spojené státy), T. KAWAI (840 Spojené státy), J. E. WALTER (840 Spojené státy), I.V. KONDRATENKO (643 Rusko), A. SEDIVA (203 Česká republika), M. VAN DER BURG (528 Nizozemské království), N. B. KUZMENKO (643 Rusko), L. D. NOTARANGELO (840 Spojené státy), E. BERNATOWSKA (616 Polsko) a O. V. ALEINIKOVA (112 Bělorusko).
Vydání Frontiers in Immunology, LAUSANNE, FRONTIERS MEDIA SA, 2020, 1664-3224.
Další údaje
Originální jazyk angličtina
Typ výsledku Článek v odborném periodiku
Obor 30102 Immunology
Stát vydavatele Švýcarsko
Utajení není předmětem státního či obchodního tajemství
WWW URL
Impakt faktor Impact factor: 7.561
Kód RIV RIV/00216224:14110/20:00116171
Organizační jednotka Lékařská fakulta
Doi http://dx.doi.org/10.3389/fimmu.2020.00900
UT WoS 000546856100001
Klíčová slova anglicky RAG1; RAG2; primary immunodeficiency; geographic distribution; incidence; Slavic children
Štítky 14110114, rivok
Příznaky Mezinárodní význam, Recenzováno
Změnil Změnila: Mgr. Tereza Miškechová, učo 341652. Změněno: 10. 8. 2020 12:52.
Anotace
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 theRAGdefects in populations inhabiting South, West, and East Slavic countries. Methods:Demographic, clinical, and laboratory data were collected fromRAG-deficient patients of Slavic origin via chart review, retrospectively. Recombinase activity was determinedin vitroby flow cytometry-based assay. Results:Based on the clinical and immunologic phenotype, our cohort of 82 patients from 68 families represented a wide spectrum ofRAGdeficiencies, including SCID (n= 20), OS (n= 37), and LS/CID (n= 25) phenotypes. Sixty-seven (81.7%) patients carriedRAG1and 15 patients (18.3%) carriedRAG2biallelic variants. We estimate that the minimal annual incidence ofRAGdeficiency 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 withRAG1variants 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 homozygousRAG1p.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 homozygousRAG1p.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 thatRAG1p.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 ofRAG1founder 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.
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