title: Of genes and phenotypes: the immunological and molecular spectrum of combined immune deficiency. Defects of the gamma(c)-JAK3 signaling pathway as a model.
abstract: Cytokines play a major role in lymphoid development. Defects of the common gamma chain (gamma(c)) or of the JAK3 protein in humans have been shown to result in a severe combined immune deficiency (SCID), with a profound defect in T and natural killer (NK)-cell development, whereas B-cell generation is apparently unaffected (T-B+NK-SCID). While extensive molecular and biochemical analysis of these patients has been instrumental in understanding better the biological properties of the gamma(c) and JAK3 protein, an unexpected phenotypic heterogeneity of gamma(c) and JAK3 deficiency has emerged, indicating the need for appropriate and extensive investigations even in patients with atypical presentations. At the same time, characterization of the defects has been instrumental in the development of novel therapeutic approaches, from in utero hematopoietic stem cell transplantation to gene therapy.
authors.affiliation: Istituto di Medicina Molecolare Angelo Nocivelli, Clinica Pediatrica, Università di Brescia, Italy. notarang@master.cci.unibs.it
authors.forename: L D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: S
authors.initials: S
authors.lastname: Giliani
authors.forename: C
authors.initials: C
authors.lastname: Mazza
authors.forename: P
authors.initials: P
authors.lastname: Mella
authors.forename: G
authors.initials: G
authors.lastname: Savoldi
authors.forename: C
authors.initials: C
authors.lastname: Rodriguez-Pérez
authors.forename: E
authors.initials: E
authors.lastname: Mazzolari
authors.forename: M
authors.initials: M
authors.lastname: Fiorini
authors.forename: M
authors.initials: M
authors.lastname: Duse
authors.forename: A
authors.initials: A
authors.lastname: Plebani
authors.forename: A G
authors.initials: AG
authors.lastname: Ugazio
authors.forename: M
authors.initials: M
authors.lastname: Vihinen
authors.forename: F
authors.initials: F
authors.lastname: Candotti
authors.forename: R F
authors.initials: RF
authors.lastname: Schumacher
mesh_terms: D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D053616:Janus Kinase 3; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines; D015375:Receptors, Interleukin-2; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3