Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID)

Paolo Macchi, Anna Villa, Silvia Giliani, Maria G. Sacco, Annalisa Frattini, Fulvio Porta, Alberto G. Ugazio, James A. Johnston, Fabio Candotti, John J. O'Shea, Paolo Vezzoni, Luigi D. Notarangelo

Research output: Contribution to journalArticlepeer-review


Severe combined immune deficiency (SCID) represents a heterogenous group of hereditary diseases. Mutations in the common γ-chain (γ(c)), which is part of several cytokine receptors including those for interleukin (IL)-2, IL-4, IL-7, IL-9 and IL-15, are responsible for X-linked SCID, which is usually associated with a lack of circulating T cells and the presence of B lymphocytes (T-B+ SCID). The gene(s) responsible for autosomal recessive T-B+ SCID is still unknown. The Jak-3 protein kinase has been found to associate with the γ(c)-chain-containing cytokine receptors. Therefore Jak-3 or other STAT proteins with which it interacts are candidate genes for autosomal recessive T-B+ SCID. Here we investigate two unrelated T-B+ SCID patients (both from consanguineous parents) who have homozygous mutations in the gene for Jak-3. One patient carries a mutation (Tyr100 → Cys) in a conserved tyrosine residue in the JH7 domain of Jak-3 which is absent in more than 150 investigated chromosomes. The other patient carries a homozygous 151-base-pair deletion in the kinase-like domain, leading to a frameshift and premature termination. Both mutations resulted in markedly reduced levels of Jak-3. These findings show that abnormalities in the Jak/STAT signalling pathway can account for SCID in humans.

Original languageEnglish
Pages (from-to)65-68
Number of pages4
Issue number6544
Publication statusPublished - Sept 7 1995

ASJC Scopus subject areas

  • General


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