title: Complete genomic organization of the human JAK3 gene and mutation analysis in severe combined immunodeficiency by single-strand conformation polymorphism.
abstract: JAK3 deficiency in humans results in autosomal recessive T-B+ severe combined immunodeficiency disease (SCID), a severe immunodeficiency that can only be cured by bone marrow transplantation. We unraveled the complete organization of the human JAK3 gene, which includes 23 exons. This information allowed us to set up a molecular screening test that enabled us to diagnose JAK3 deficiency in 14 patients from 12 unrelated families with T-B+ SCID. In order to define the mutations, we used a nonradioactive single-strand conformation polymorphism (SSCP)/heteroduplex (HD) assay based on exon-specific polymerase chain reaction (PCR). In this cohort of patients, 15 independent JAK3 gene mutations have been identified, including 7 that have not been described previously. Mutation analysis information was used for genetic counseling and prenatal diagnosis.
authors.affiliation: Clinica Pediatrica dell'Università degli Studi di Brescia and Istituto di Medicina Molecolare Angelo Nocivelli, Italy. schumach@master.cci.unibs.it
authors.forename: R F
authors.initials: RF
authors.lastname: Schumacher
authors.forename: P
authors.initials: P
authors.lastname: Mella
authors.forename: R
authors.initials: R
authors.lastname: Badolato
authors.forename: M
authors.initials: M
authors.lastname: Fiorini
authors.forename: G
authors.initials: G
authors.lastname: Savoldi
authors.forename: S
authors.initials: S
authors.lastname: Giliani
authors.forename: A
authors.initials: A
authors.lastname: Villa
authors.forename: F
authors.initials: F
authors.lastname: Candotti
authors.forename: A
authors.initials: A
authors.lastname: Tampalini
authors.forename: J J
authors.initials: JJ
authors.lastname: O'Shea
authors.forename: L D
authors.initials: LD
authors.lastname: Notarangelo
mesh_terms: D003241:Consanguinity; D004252:DNA Mutational Analysis / Q000379:methods*; D005091:Exons; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns; D053616:Janus Kinase 3; D008297:Male; D008957:Models, Genetic; D008969:Molecular Sequence Data; D018807:Polymorphism, Single-Stranded Conformational; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000235:genetics*
chemical_list: D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3