FORMANKOVA, Renata, Veronika KANDEROVA, Marketa RACKOVA, Michael SVATON, Tomas BRDICKA, Petr RIHA, Petra KESLOVÁ, Ester MEJSTRIKOVA, Marketa ZALIOVA, Tomáš FREIBERGER, Hana GROMBIŘÍKOVÁ, Zuzana ZEMANOVA, Marcela VLKOVÁ, Filip FENCL, Ivana COPOVA, Jiri BRONSKY, Petr JABANDŽIEV, Petr SEDLACEK, Jana ŠOUKALOVÁ, Ondrej ZAPLETAL, Jan STARY, Jan TRKA, Tomas KALINA, Karolina KRAMARZOVA, Eva HLAVÁČKOVÁ, Jiří LITZMAN and Eva FRONKOVA. Novel SAMD9 Mutation in a Patient With Immunodeficiency, Neutropenia, Impaired Anti-CMV Response, and Severe Gastrointestinal Involvement. Frontiers in Immunology. LAUSANNE: FRONTIERS MEDIA SA, 2019, vol. 10, SEP 18 2019, p. 1-8. ISSN 1664-3224. doi:10.3389/fimmu.2019.02194.
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Basic information
Original name Novel SAMD9 Mutation in a Patient With Immunodeficiency, Neutropenia, Impaired Anti-CMV Response, and Severe Gastrointestinal Involvement
Authors FORMANKOVA, Renata (203 Czech Republic), Veronika KANDEROVA (203 Czech Republic), Marketa RACKOVA (203 Czech Republic), Michael SVATON (203 Czech Republic), Tomas BRDICKA (203 Czech Republic), Petr RIHA (203 Czech Republic), Petra KESLOVÁ (203 Czech Republic), Ester MEJSTRIKOVA (203 Czech Republic), Marketa ZALIOVA (203 Czech Republic), Tomáš FREIBERGER (203 Czech Republic, belonging to the institution), Hana GROMBIŘÍKOVÁ (203 Czech Republic, belonging to the institution), Zuzana ZEMANOVA (203 Czech Republic), Marcela VLKOVÁ (203 Czech Republic, belonging to the institution), Filip FENCL (203 Czech Republic), Ivana COPOVA (203 Czech Republic), Jiri BRONSKY (203 Czech Republic), Petr JABANDŽIEV (203 Czech Republic, belonging to the institution), Petr SEDLACEK (203 Czech Republic), Jana ŠOUKALOVÁ (203 Czech Republic, belonging to the institution), Ondrej ZAPLETAL (203 Czech Republic), Jan STARY (203 Czech Republic), Jan TRKA (203 Czech Republic), Tomas KALINA (203 Czech Republic), Karolina KRAMARZOVA (203 Czech Republic), Eva HLAVÁČKOVÁ (203 Czech Republic, belonging to the institution), Jiří LITZMAN (203 Czech Republic, belonging to the institution) and Eva FRONKOVA (203 Czech Republic, guarantor).
Edition Frontiers in Immunology, LAUSANNE, FRONTIERS MEDIA SA, 2019, 1664-3224.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30102 Immunology
Country of publisher Switzerland
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 5.085
RIV identification code RIV/00216224:14110/19:00111013
Organization unit Faculty of Medicine
UT WoS 000486387300001
Keywords in English SAMD9; MIRAGE; immunodeficiency; neutropenia; cytomegalovirus infection; dysphagia; hematopoietic stem cell transplantation; gastrointestinal disorder
Tags 14110114, 14110317, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Tereza Miškechová, učo 341652. Changed: 26/3/2021 09:40.
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. Conclusion: We describe a novel SAMD9 mutation in a patient with prominent gastrointestinal and immunological symptoms but without adrenal hypoplasia. Thus, SAMD9 mutations should be considered as cause of enteropathy in pediatric patients. The insufficient therapeutic outcome of transplantation further questions the role of HSCT in the management of patients with SAMD9 mutations and multisystem involvement.
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