@article{2999962,
    title = "Case Report: A Novel Synonymous ARPC1B Gene Mutation Causes a Syndrome of Combined Immunodeficiency, Asthma, and Allergy With Significant Intrafamilial Clinical Heterogeneity",
    author = "Papadatou, I. and Marinakis, N. and Botsa, E. and Tzanoudaki, M. and Kanariou, M. and Orfanou, I. and Kanaka-Gantenbein, C. and Traeger-Synodinos, J. and Spoulou, V.",
    journal = "Frontiers in Immunology",
    year = "2021",
    volume = "12",
    publisher = "Frontiers Media S.A",
    doi = "10.3389/fimmu.2021.634313",
    keywords = "C reactive protein;  CD19 antigen;  CD3 antigen;  ceftazidime;  clindamycin;  cotrimoxazole;  epinephrine;  fluticasone;  ganciclovir;  immunoglobulin A;  immunoglobulin E;  immunoglobulin G;  immunoglobulin M;  leukocyte antigen;  messenger RNA;  montelukast;  piperacillin plus tazobactam;  teicoplanin;  actin related protein 2-3 complex;  ARPC1B protein, human, adolescent;  allergy;  allogeneic hematopoietic stem cell transplantation;  ARPC1B gene;  Article;  asthma;  autoimmunity;  case report;  CD4+ T lymphocyte;  CD8+ T lymphocyte;  cell heterogeneity;  cell migration;  cell proliferation;  cell transplantation;  central nervous system;  child;  clinical article;  cytoskeleton;  diet therapy;  eczema;  exophthalmos;  female;  gene;  gene mutation;  genetic association;  hematopoietic cell;  hematopoietic stem cell transplantation;  high throughput sequencing;  hospitalization;  human;  hypothyroidism;  immune deficiency;  immunization;  infant;  interferon gamma release assay;  leukocytosis;  lower respiratory tract infection;  lymphadenopathy;  male;  microcytic anemia;  mortality;  multiplex polymerase chain reaction;  phenotype;  polymerase chain reaction;  protein structure;  Pseudomonas aeruginosa;  recurrent infection;  respiratory tract infection;  Sanger sequencing;  school child;  tachycardia;  Th17 cell;  tuberculosis;  umbilical cord;  wheezing;  asthma;  genetic predisposition;  genetics;  heredity;  homozygote;  hypersensitivity;  immunology;  mutation;  pedigree;  RNA splicing;  syndrome;  treatment outcome, Actin-Related Protein 2-3 Complex;  Adolescent;  Asthma;  Child;  Female;  Genetic Predisposition to Disease;  Hematopoietic Stem Cell Transplantation;  Heredity;  Homozygote;  Humans;  Hypersensitivity;  Infant;  Male;  Mutation;  Pedigree;  Phenotype;  Primary Immunodeficiency Diseases;  RNA Splicing;  Syndrome;  Treatment Outcome",
    abstract = "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. © Copyright © 2021 Papadatou, Marinakis, Botsa, Tzanoudaki, Kanariou, Orfanou, Kanaka-Gantenbein, Traeger-Synodinos and Spoulou."
}