@article{7654d7a4374245548af972dc05611386,
title = "Immunodeficiency with susceptibility to lymphoma with complex genotype affecting energy metabolism (FBP1, ACAD9) and vesicle trafficking (RAB27A)",
abstract = "Introduction: Inborn errors of immunity (IEI) are characterized by a dysfunction of the immune system leading to increased susceptibility to infections, impaired immune regulation and cancer. We present a unique consanguineous family with a history of Hodgkin lymphoma, impaired EBV control and a late onset hemophagocytic lymphohistiocytosis (HLH). Methods and results: Overall, family members presented with variable impairment of NK cell and cytotoxic T cell degranulation and cytotoxicity. Exome sequencing identified homozygous variants in RAB27A, FBP1 (Fructose-1,6-bisphosphatase 1) and ACAD9 (Acyl-CoA dehydrogenase family member 9). Variants in RAB27A lead to Griscelli syndrome type 2, hypopigmentation and HLH predisposition. Discussion: Lymphoma is frequently seen in patients with hypomorphic mutations of genes predisposing to HLH. We hypothesize that the variants in FBP1 and ACAD9 might aggravate the clinical and immune phenotype, influence serial killing and lytic granule polarization by CD8 T cells. Understanding of the interplay between the multiple variants identified by whole exome sequencing (WES) is essential for correct interpretation of the immune phenotype and important for critical treatment decisions.",
keywords = "Lymphoma, RAB27A-deficiency, Griscelli-syndrome, Epstein-Barr virus, metabolic diseases, Griscelli syndrome type 2, lymphoma",
author = "Nina Brauer and Yuto Maruta and Miriam Lisci and Katharina Strege and Ilske Oschlies and Hikari Nakamura and Svea B{\"o}hm and Kai Lehmberg and Leon Brandhoff and Stephan Ehl and Nima Parvaneh and Wolfram Kappler and Mitsunori Fukuda and Griffiths, {Gillian M.} and Hans Hennies and Tim Niehues and Ammann, {Sandra K.}",
note = "Funding Information: This study was supported by the SFB 1160/IMPATH of the German Research Foundation (DFG) by the German Federal Ministry of Education and Research (BMBF 01 EO 0803 grant to the Center of Chronic Immunodeficiency) and Deutsche Kinderkrebsstiftung (DKS 2018.11). This work was supported in part by a Grant-in-Aid for Scientific Research (B) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (grant number 22H02613 to MF), Japan Science and Technology Agency (JST) CREST (grant number JPMJCR17H4 to M.F.), and by the Japan Society for the Promotion of Science (JSPS) (to YM). Publisher Copyright: Copyright {\textcopyright} 2023 Brauer, Maruta, Lisci, Strege, Oschlies, Nakamura, B{\"o}hm, Lehmberg, Brandhoff, Ehl, Parvaneh, Klapper, Fukuda, Griffiths, Hennies, Niehues and Ammann.",
year = "2023",
month = jun,
day = "14",
doi = "10.3389/fimmu.2023.1151166",
language = "English",
volume = "14",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S.A.",
}