PMID- 33679784 OWN - NLM STAT- MEDLINE DCOM- 20210921 LR - 20210921 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - Case Report: A Novel Synonymous ARPC1B Gene Mutation Causes a Syndrome of Combined Immunodeficiency, Asthma, and Allergy With Significant Intrafamilial Clinical Heterogeneity. PG - 634313 LID - 10.3389/fimmu.2021.634313 [doi] LID - 634313 AB - Recently, a novel syndrome of combined immune deficiency, infections, allergy, and inflammation has been attributed to mutations in the gene encoding actin-related protein 2/3 complex subunit 1B (ARPC1B), which is a key molecule driving the dynamics of the cytoskeleton. Homozygous mutations in the ARPC1B gene have been found to result in the disruption of the protein structure and cause an autosomal recessive syndrome of combined immune deficiency, impaired T-cell migration and proliferation, increased levels of immunoglobulin E (IgE) and immunoglobulin A (IgA), and thrombocytopenia. To date, only a few individuals have been diagnosed with the ARPC1B deficiency syndrome worldwide. In this case series, we report the wide spectrum of phenotype in 3 siblings of a consanguineous family from Afghanistan with a novel homozygous synonymous pathogenic variant c.783G>A, p. (Ala261Ala) of the ARPC1B gene that causes a similar syndrome but no thrombocytopenia. Targeted RNA studies demonstrated that the variant affects the splicing process of mRNA, resulting in a marked reduction of the levels of primary (normal) RNA transcript of the ARPC1B gene in the affected patients and likely premature termination from the abnormally spliced mRNA. The next generation sequencing (NGS) studies facilitated the diagnosis of this rare combined immunodeficiency and led to the decision to treat the affected patients with hematopoietic cell transplant (HCT) from an human leukocyte antigen (HLA)-matched healthy sibling. CI - Copyright (c) 2021 Papadatou, Marinakis, Botsa, Tzanoudaki, Kanariou, Orfanou, Kanaka-Gantenbein, Traeger-Synodinos and Spoulou. FAU - Papadatou, Ioanna AU - Papadatou I AD - First Department of Paediatrics, Medical School, "Aghia Sophia" Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece. AD - Immunobiology and Vaccinology Research Lab, First Department of Paediatrics, Medical School, National and Kapodistrian University of Athens, Athens, Greece. AD - University Research Institute of Maternal and Child Health and Precision Medicine, "Aghia Sophia" Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece. FAU - Marinakis, Nikolaos AU - Marinakis N AD - University Research Institute of Maternal and Child Health and Precision Medicine, "Aghia Sophia" Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece. AD - Laboratory of Medical Genetics, "Aghia Sophia" Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece. FAU - Botsa, Evanthia AU - Botsa E AD - First Department of Paediatrics, Medical School, "Aghia Sophia" Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece. FAU - Tzanoudaki, Marianna AU - Tzanoudaki M AD - Department of Immunology and Histocompatibility, Specialized Center and Referral Center for Primary Immunodeficiencies, Paediatric Immunology, "Aghia Sophia" Children's Hospital, Athens, Greece. FAU - Kanariou, Maria AU - Kanariou M AD - Department of Immunology and Histocompatibility, Specialized Center and Referral Center for Primary Immunodeficiencies, Paediatric Immunology, "Aghia Sophia" Children's Hospital, Athens, Greece. FAU - Orfanou, Irene AU - Orfanou I AD - First Department of Paediatrics, Medical School, "Aghia Sophia" Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece. FAU - Kanaka-Gantenbein, Christina AU - Kanaka-Gantenbein C AD - First Department of Paediatrics, Medical School, "Aghia Sophia" Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece. FAU - Traeger-Synodinos, Joanne AU - Traeger-Synodinos J AD - Laboratory of Medical Genetics, "Aghia Sophia" Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece. FAU - Spoulou, Vana AU - Spoulou V AD - First Department of Paediatrics, Medical School, "Aghia Sophia" Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece. AD - Immunobiology and Vaccinology Research Lab, First Department of Paediatrics, Medical School, National and Kapodistrian University of Athens, Athens, Greece. LA - eng PT - Case Reports PT - Research Support, Non-U.S. Gov't DEP - 20210219 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (ARPC1B protein, human) RN - 0 (Actin-Related Protein 2-3 Complex) SB - IM MH - Actin-Related Protein 2-3 Complex/*genetics MH - Adolescent MH - Asthma/diagnosis/*genetics/immunology/surgery MH - Child MH - Female MH - Genetic Predisposition to Disease MH - Hematopoietic Stem Cell Transplantation MH - Heredity MH - Homozygote MH - Humans MH - Hypersensitivity/diagnosis/*genetics/immunology/surgery MH - Infant MH - Male MH - *Mutation MH - Pedigree MH - Phenotype MH - Primary Immunodeficiency Diseases/diagnosis/*genetics/immunology/surgery MH - RNA Splicing MH - Syndrome MH - Treatment Outcome PMC - PMC7933039 OTO - NOTNLM OT - Arpc1b OT - allergy OT - case report OT - combined immune deficiency OT - immunodeficiency OT - inborn errors of immunity COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/03/09 06:00 MHDA- 2021/09/22 06:00 PMCR- 2021/01/01 CRDT- 2021/03/08 05:50 PHST- 2020/11/27 00:00 [received] PHST- 2021/01/26 00:00 [accepted] PHST- 2021/03/08 05:50 [entrez] PHST- 2021/03/09 06:00 [pubmed] PHST- 2021/09/22 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.634313 [doi] PST - epublish SO - Front Immunol. 2021 Feb 19;12:634313. doi: 10.3389/fimmu.2021.634313. eCollection 2021.