title: Deep intronic mis-splicing mutation in JAK3 gene underlies T-B+NK- severe combined immunodeficiency phenotype.
abstract: Severe combined immune deficiency (SCID) is a group of genetically heterogeneous diseases caused by an early block in T cell differentiation and present with life threatening infections, often within the first year of life. Janus kinase (JAK)3 gene mutations have been found to cause autosomal recessive T-B+ SCID phenotype. In this study we describe three patients with a novel deep intronic mis-splicing mutation in JAK3 as a cause of T-B+NK- SCID highlighting the need for careful evaluation of intronic regulatory elements of known genes associated with clearly defined clinical phenotypes. We present the cases and discuss the current literature.
authors.affiliation: Pediatric Hematology/Oncology and Bone Marrow Transplantation, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Electronic address: polina@hadassah.org.il.
authors.forename: Polina
authors.initials: P
authors.lastname: Stepensky
authors.affiliation: Center for Chronic Immunodeficiency, University Medical Center and University of Freiburg, Freiburg, Germany.
authors.forename: Baerbel
authors.initials: B
authors.lastname: Keller
authors.affiliation: Pediatric Division, Hadassah-Hebrew University Medical Center, Ein Kerem, Jerusalem, Israel.
authors.forename: Oded
authors.initials: O
authors.lastname: Shamriz
authors.affiliation: Pediatric Division, Hadassah-Hebrew University Medical Center, Ein Kerem, Jerusalem, Israel.
authors.forename: Adeeb
authors.initials: A
authors.lastname: NaserEddin
authors.affiliation: Pediatric Department, Makassed Hospital, Jerusalem, Israel.
authors.forename: Nisreen
authors.initials: N
authors.lastname: Rumman
authors.affiliation: Pediatric Hematology/Oncology and Bone Marrow Transplantation, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Weintraub
authors.affiliation: Center for Chronic Immunodeficiency, University Medical Center and University of Freiburg, Freiburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Warnatz
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Orly
authors.initials: O
authors.lastname: Elpeleg
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Yaacov
authors.initials: Y
authors.lastname: Barak
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D003241:Consanguinity; D005260:Female; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics*; D053616:Janus Kinase 3 / Q000235:genetics* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D009154:Mutation; D010641:Phenotype; D012326:RNA Splicing / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C507933:JAK3 protein, human; D053616:Janus Kinase 3
keywords: JAK3; Mis-splicing mutations; SCID