Mutations in severe combined immune deficiency (SCID) due to JAK3 deficiency

Human MutationVolume 18, Issue 4 p. 255-263 Mutation Update Mutations in severe combined immune deficiency (SCID) due to JAK3 deficiency Luigi D. Notarangelo, Corresponding Author Luigi D. Notarangelo notarang@master.cci.unibs.it Istituto di Medicina Molecolare “Angelo Nocivelli,” Department of Pediatrics, University of Brescia, Brescia, ItalyDepartment of Pediatrics, University of Brescia, Spedali Civili, 25123 Brescia, ItalySearch for more papers by this authorPatrizia Mella, Patrizia Mella Istituto di Medicina Molecolare “Angelo Nocivelli,” Department of Pediatrics, University of Brescia, Brescia, ItalySearch for more papers by this authorAlison Jones, Alison Jones Hospital for Sick Children, London, England, UKSearch for more papers by this authorGenevieve de Saint Basile, Genevieve de Saint Basile Inserm U 429, Hopital Necker, Paris, FranceSearch for more papers by this authorGianfranco Savoldi, Gianfranco Savoldi Istituto di Medicina Molecolare “Angelo Nocivelli,” Department of Pediatrics, University of Brescia, Brescia, ItalySearch for more papers by this authorTreena Cranston, Treena Cranston Hospital for Sick Children, London, England, UKSearch for more papers by this authorMauno Vihinen, Mauno Vihinen Institute of Medical Technology, University of Tampere, Tampere, Finland Tampere University Hospital, Tampere, FinlandSearch for more papers by this authorRichard Fabian Schumacher, Richard Fabian Schumacher Istituto di Medicina Molecolare “Angelo Nocivelli,” Department of Pediatrics, University of Brescia, Brescia, ItalySearch for more papers by this author Luigi D. Notarangelo, Corresponding Author Luigi D. Notarangelo notarang@master.cci.unibs.it Istituto di Medicina Molecolare “Angelo Nocivelli,” Department of Pediatrics, University of Brescia, Brescia, ItalyDepartment of Pediatrics, University of Brescia, Spedali Civili, 25123 Brescia, ItalySearch for more papers by this authorPatrizia Mella, Patrizia Mella Istituto di Medicina Molecolare “Angelo Nocivelli,” Department of Pediatrics, University of Brescia, Brescia, ItalySearch for more papers by this authorAlison Jones, Alison Jones Hospital for Sick Children, London, England, UKSearch for more papers by this authorGenevieve de Saint Basile, Genevieve de Saint Basile Inserm U 429, Hopital Necker, Paris, FranceSearch for more papers by this authorGianfranco Savoldi, Gianfranco Savoldi Istituto di Medicina Molecolare “Angelo Nocivelli,” Department of Pediatrics, University of Brescia, Brescia, ItalySearch for more papers by this authorTreena Cranston, Treena Cranston Hospital for Sick Children, London, England, UKSearch for more papers by this authorMauno Vihinen, Mauno Vihinen Institute of Medical Technology, University of Tampere, Tampere, Finland Tampere University Hospital, Tampere, FinlandSearch for more papers by this authorRichard Fabian Schumacher, Richard Fabian Schumacher Istituto di Medicina Molecolare “Angelo Nocivelli,” Department of Pediatrics, University of Brescia, Brescia, ItalySearch for more papers by this author First published: 18 September 2001 https://doi.org/10.1002/humu.1188Citations: 69AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract During the last 10 years, an increasing number of genes have been identified whose abnormalities account for primary immunodeficiencies, with defects in development and/or function of the immune system. Among them is the JAK3-gene, encoding for a tyrosine kinase that is functionally coupled to cytokine receptors which share the common gamma chain. Defects of this gene cause an autosomal recessive form of severe combined immunodeficiency with almost absent T-cells and functionally defective B-cells (T–B+ SCID). Herewith, we present molecular information on the first 27 unique mutations identified in the JAK3 gene, including clinical data on all of the 23 affected patients reported so far. A variety of mutations scattered throughout all seven functional domains of the protein, and with different functional effects, have been identified. Availability of a molecular screening test, based on amplification of genomic DNA, facilitates the diagnostic approach, and has permitted recognition that JAK3 deficiency may also be associated with atypical clinical and immunological features. Development of a structural model of the JAK3 kinase domain has allowed characterization of the functional effects of the various mutations. Most importantly, molecular analysis at the JAK3 locus results in improved genetic counseling, allows early prenatal diagnosis, and prompts appropriate treatment (currently based on hematopoietic stem cell transplantation) in affected families. Hum Mutat 18:255–263, 2001. © 2001 Wiley-Liss, Inc. Citing Literature Volume18, Issue4October 2001Pages 255-263 RelatedInformation