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@article{1572137,
author = {Formankova, Renata and Kanderova, Veronika and Rackova, Marketa and Svaton, Michael and Brdicka, Tomas and Riha, Petr and Keslová, Petra and Mejstrikova, Ester and Zaliova, Marketa and Freiberger, Tomáš and Grombiříková, Hana and Zemanova, Zuzana and Vlková, Marcela and Fencl, Filip and Copova, Ivana and Bronsky, Jiri and Jabandžiev, Petr and Sedlacek, Petr and Šoukalová, Jana and Zapletal, Ondrej and Stary, Jan and Trka, Jan and Kalina, Tomas and Kramarzova, Karolina and Hlaváčková, Eva and Litzman, Jiří and Fronkova, Eva},
article_location = {LAUSANNE},
article_number = {SEP 18 2019},
doi = {http://dx.doi.org/10.3389/fimmu.2019.02194},
keywords = {SAMD9; MIRAGE; immunodeficiency; neutropenia; cytomegalovirus infection; dysphagia; hematopoietic stem cell transplantation; gastrointestinal disorder},
language = {eng},
issn = {1664-3224},
journal = {Frontiers in Immunology},
title = {Novel SAMD9 Mutation in a Patient With Immunodeficiency, Neutropenia, Impaired Anti-CMV Response, and Severe Gastrointestinal Involvement},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2019.02194/full},
volume = {10},
year = {2019}
}
TY - JOUR
ID - 1572137
AU - Formankova, Renata - Kanderova, Veronika - Rackova, Marketa - Svaton, Michael - Brdicka, Tomas - Riha, Petr - Keslová, Petra - Mejstrikova, Ester - Zaliova, Marketa - Freiberger, Tomáš - Grombiříková, Hana - Zemanova, Zuzana - Vlková, Marcela - Fencl, Filip - Copova, Ivana - Bronsky, Jiri - Jabandžiev, Petr - Sedlacek, Petr - Šoukalová, Jana - Zapletal, Ondrej - Stary, Jan - Trka, Jan - Kalina, Tomas - Kramarzova, Karolina - Hlaváčková, Eva - Litzman, Jiří - Fronkova, Eva
PY - 2019
TI - Novel SAMD9 Mutation in a Patient With Immunodeficiency, Neutropenia, Impaired Anti-CMV Response, and Severe Gastrointestinal Involvement
JF - Frontiers in Immunology
VL - 10
IS - SEP 18 2019
SP - 1-8
EP - 1-8
PB - FRONTIERS MEDIA SA
SN - 16643224
KW - SAMD9
KW - MIRAGE
KW - immunodeficiency
KW - neutropenia
KW - cytomegalovirus infection
KW - dysphagia
KW - hematopoietic stem cell transplantation
KW - gastrointestinal disorder
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2019.02194/full
L2 - https://www.frontiersin.org/articles/10.3389/fimmu.2019.02194/full
N2 - 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.
ER -
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. \textit{Frontiers in Immunology}. LAUSANNE: FRONTIERS MEDIA SA, vol.~10, SEP 18 2019, p.~1-8. ISSN~1664-3224. doi:10.3389/fimmu.2019.02194. 2019.
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