title: Diverse phenotypic and genotypic presentation of RAG1 mutations in two cases with SCID.
abstract: Severe combined immunodeficiencies (SCID) comprise a spectrum of genetic defects that involve both humoral and cellular immunities. Defects in recombinating activating gene 1 (RAG1), RAG2, Artemis, or LIG4 can disrupt V(D)J recombination. Defective V(D)J recombination of the T and B cell receptors is responsible for T(-)B(-)NK(+)SCID. Amorphic mutations in RAG1 and RAG2 cause T(-)B(-)NK(+)SCID, whereas hypomorphic mutations cause an immunodeficency characterized by oligoclonal expansion of TCRgammadelta T cells, severe CMV infection and autoimmunity. First patient is a typical T(-)B(-)NK(+)SCID with clinical and immunologic findings while the second is atypical with normal immunoglobulin levels, CD4 lymphopenia, elevated TCRgammadelta T cells, persistent CMV infection, and autoimmune hemolytic anemia. These cases are presented to emphasize that mutations in RAG1 gene may lead to a diverse spectrum of clinical and immunologic findings while hypomorphic mutations may be related with autoimmunity and refractory CMV infection during infancy.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Ege University, 35100, Bornova, Izmir, Turkey. neslihanedeer@yahoo.com
authors.forename: Neslihan Edeer
authors.initials: NE
authors.lastname: Karaca
authors.forename: Guzide
authors.initials: G
authors.lastname: Aksu
authors.forename: Ferah
authors.initials: F
authors.lastname: Genel
authors.forename: Nesrin
authors.initials: N
authors.lastname: Gulez
authors.forename: Sema
authors.initials: S
authors.lastname: Can
authors.forename: Yesim
authors.initials: Y
authors.lastname: Aydinok
authors.forename: Serap
authors.initials: S
authors.lastname: Aksoylar
authors.forename: Emin
authors.initials: E
authors.lastname: Karaca
authors.forename: Imren
authors.initials: I
authors.lastname: Altuglu
authors.forename: Necil
authors.initials: N
authors.lastname: Kutukculer
mesh_terms: D002648:Child; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology / Q000628:therapy; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D012141:Respiratory Tract Infections / Q000235:genetics / Q000276:immunology / Q000628:therapy; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000628:therapy
chemical_list: D018398:Homeodomain Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C064658:RAG-1 protein