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

Research output: Contribution to journalArticle

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. (C) 2001 Wiley-Liss,Inc.

Details

Authors
  • LD Notorangelo
  • P Mella
  • A Jones
  • GD Baisle
  • G Savoldi
  • T Cranston
  • Mauno Vihinen
  • RF Schumacher
External organisations
  • External Organization - Unknown
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics

Keywords

  • tyrosine kinase, mutation database, autosomal recessive, SCID, immune deficiency, JAK3, severe combined immune deficiency, intracellular, cytokine receptor
Original languageEnglish
Pages (from-to)255-263
JournalHuman Mutation
Volume18
Issue number4
Publication statusPublished - 2001
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes