Počet záznamů: 1
Novel SAMD9 Mutation in a Patient With Immunodeficiency, Neutropenia, Impaired Anti-CMV Response, and Severe Gastrointestinal Involvement
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SYSNO ASEP 0522736 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Novel SAMD9 Mutation in a Patient With Immunodeficiency, Neutropenia, Impaired Anti-CMV Response, and Severe Gastrointestinal Involvement Tvůrce(i) Formankova, R. (CZ)
Kanderová, V. (CZ)
Rackova, M. (CZ)
Svaton, M. (CZ)
Brdička, Tomáš (UMG-J) RID
Říha, P. (CZ)
Keslova, P. (CZ)
Mejstříková, E. (CZ)
Žaliová, M. (CZ)
Freiberger, T. (CZ)
Grombirikova, H. (CZ)
Zemanová, Z. (CZ)
Vlková, M. (CZ)
Fencl, F. (CZ)
Copova, I. (CZ)
Bronsky, J. (CZ)
Jabandžiev, P. (CZ)
Sedláček, P. (CZ)
Šoukalová, J. (CZ)
Zapletal, O. (CZ)
Starý, J. (CZ)
Trka, J. (CZ)
Kalina, T. (CZ)
Kramarzova, K.S. (CZ)
Hlavackova, E. (CZ)
Litzman, J. (CZ)
Froňková, E. (CZ)Celkový počet autorů 27 Číslo článku 2194 Zdroj.dok. Frontiers in Immunology. - : Frontiers Media - ISSN 1664-3224
Roč. 10, September (2019)Poč.str. 8 s. Forma vydání Online - E Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova samd9 ; mirage ; immunodeficiency ; neutropenia ; cytomegalovirus infection ; dysphagia ; hematopoietic stem cell transplantation ; gastrointestinal disorder Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Immunology Způsob publikování Open access Institucionální podpora UMG-J - RVO:68378050 UT WOS 000486387300001 DOI 10.3389/fimmu.2019.02194 Anotace Mutations in the Sterile alpha motif domain containing 9 (SAMD9) gene have been described in patients with severe multisystem disorder, MIRAGE syndrome, but also in patients with bone marrow (BM) failure in the absence of other systemic symptoms. The role of hematopoietic stem cell transplantation (HSCT) in the management of the disease is still unclear. Here, we present a patient with a novel mutation in SAMD9 (c.2471 G >A, p.R824Q), manifesting with prominent gastrointestinal tract involvement and immunodeficiency, but without any sign of adrenal insufficiency typical for MIRAGE syndrome. He suffered from severe CMV (cytomegalovirus) infection at 3 months of age, with a delayed development of T lymphocyte functional response against CMV, profound T cell activation, significantly reduced B lymphocyte counts and impaired lymphocyte proliferative response. Cultured T cells displayed slightly lower calcium flux and decreased survival. At the age of 6 months, he developed severe neutropenia requiring G-CSF administration, and despite only mild morphological and immunophenotypical disturbances in the BM, 78% of the BM cells showed monosomy 7 at the age of 18 months. Surprisingly, T cell proliferation after CD3 stimulation and apoptosis of the cells normalized during the follow-up, possibly reflecting the gradual development of monosomy 7. Among other prominent symptoms, he had difficulty swallowing, requiring percutaneous endoscopic gastrostomy (PEG), frequent gastrointestinal infections, and perianal erosions. He suffered from repeated infections and periodic recurring fevers with the elevation of inflammatory markers. At 26 months Frontiers of age, he underwent HSCT that significantly improved hematological and immunological laboratory parameters. Nevertheless, he continued to suffer from other conditions, and subsequently, he died at day 440 post-transplant due to sepsis. Pathogenicity of this novel SAMD9 mutation was confirmed experimentally. Expression of mutant SAMD9 caused a significant decrease in proliferation and increase in cell death of the transfected cells. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2020 Elektronická adresa https://www.frontiersin.org/articles/10.3389/fimmu.2019.02194/full
Počet záznamů: 1