title: Agammaglobulinemia associated to nasal polyposis due to a hypomorphic RAG1 mutation in a 12 years old boy.
abstract: Recombination-activating gene (RAG) 1 and 2 mutations in humans cause T-B-NK+SCID and Omenn syndrome, but milder phenotypes associated with residual protein activity have been recently described. We report a male patient with a diagnosis of common variable immunodeficiency (CVID) born from non-consanguineous parents, whose immunological phenotype was characterized by severe reduction of B cells and agammaglobulinemia for which several candidate genes were excluded by targeted Sanger sequencing. Next Generation Sequencing revealed two compound heterozygous mutations in the RAG1 gene: the previously described p.R624H, and the novel p.Y728H mutation, as well as the known polymorphism p.H249R. This case reinforces the notion of large phenotypic spectrum in RAG deficiency and opens questions on the management and follow-up of these patients.
authors.affiliation: Department of Systems Medicine, "University of Rome Tor Vergata", Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cifaldi
authors.affiliation: University Department of Pediatrics, Unit of Immune and Infectious Diseases, Childrens' Hospital Bambino Gesù, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Scarselli
authors.affiliation: Department of Systems Medicine, "University of Rome Tor Vergata", Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Petricone
authors.affiliation: University Department of Pediatrics, Unit of Immune and Infectious Diseases, Childrens' Hospital Bambino Gesù, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Cesare
authors.affiliation: University Department of Pediatrics, Unit of Immune and Infectious Diseases, Childrens' Hospital Bambino Gesù, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Chiriaco
authors.affiliation: University Department of Pediatrics, Unit of Immune and Infectious Diseases, Childrens' Hospital Bambino Gesù, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Claps
authors.affiliation: Department of Systems Medicine, "University of Rome Tor Vergata", Rome, Italy; University Department of Pediatrics, Unit of Immune and Infectious Diseases, Childrens' Hospital Bambino Gesù, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossi
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Enrica
authors.initials: E
authors.lastname: Calzoni
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
authors.forename: Luigi Daniele
authors.initials: LD
authors.lastname: Notarangelo
authors.affiliation: Department of Systems Medicine, "University of Rome Tor Vergata", Rome, Italy.
authors.forename: Gigliola
authors.initials: G
authors.lastname: Di Matteo
authors.affiliation: Department of Systems Medicine, "University of Rome Tor Vergata", Rome, Italy; University Department of Pediatrics, Unit of Immune and Infectious Diseases, Childrens' Hospital Bambino Gesù, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Cancrini
authors.affiliation: Department of Systems Medicine, "University of Rome Tor Vergata", Rome, Italy; University Department of Pediatrics, Unit of Immune and Infectious Diseases, Childrens' Hospital Bambino Gesù, Italy. Electronic address: andrea.finocchi@uniroma2.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Finocchi
mesh_terms: D000361:Agammaglobulinemia / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D009298:Nasal Polyps / Q000235:genetics* / Q000276:immunology; D010641:Phenotype
chemical_list: D018398:Homeodomain Proteins; C064658:RAG-1 protein
keywords: EBV viremia; Humoral defect; Hypomorphic mutation; RAG1