RGD Reference Report - Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). - Rat Genome Database

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

Authors: Macchi, P  Villa, A  Giliani, S  Sacco, MG  Frattini, A  Porta, F  Ugazio, AG  Johnston, JA  Candotti, F  O'Shea, JJ 
Citation: Macchi P, etal., Nature. 1995 Sep 7;377(6544):65-8.
RGD ID: 1600254
Pubmed: PMID:7659163   (View Abstract at PubMed)
DOI: DOI:10.1038/377065a0   (Journal Full-text)

Severe combined immune deficiency (SCID) represents a heterogenous group of hereditary diseases. Mutations in the common gamma-chain (gamma 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 gamma 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Jak3  (Janus kinase 3)

Genes (Mus musculus)
Jak3  (Janus kinase 3)

Genes (Homo sapiens)
JAK3  (Janus kinase 3)


Additional Information