Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID)
Details
Serval ID
serval:BIB_BBE5389EC071
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID)
Journal
Nature
Working group(s)
et al.
ISSN
0028-0836 (Print)
ISSN-L
0028-0836
Publication state
Published
Issued date
1995
Volume
377
Number
6544
Pages
65-8
Language
english
Notes
Macchi, P
Villa, A
Giliani, S
Sacco, M G
Frattini, A
Porta, F
Ugazio, A G
Johnston, J A
Candotti, F
O'Shea, J J
eng
Research Support, Non-U.S. Gov't
England
Nature. 1995 Sep 7;377(6544):65-8.
Villa, A
Giliani, S
Sacco, M G
Frattini, A
Porta, F
Ugazio, A G
Johnston, J A
Candotti, F
O'Shea, J J
eng
Research Support, Non-U.S. Gov't
England
Nature. 1995 Sep 7;377(6544):65-8.
Abstract
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.
Keywords
B-Lymphocytes/immunology, Base Sequence, Cell Line, Transformed, DNA Mutational Analysis, DNA Primers, Humans, Janus Kinase 3, Molecular Sequence Data, *Mutation, Polymerase Chain Reaction, Protein-Tyrosine Kinases/deficiency/*genetics, Sequence Deletion, Severe Combined Immunodeficiency/enzymology/*genetics/immunology, T-Lymphocytes/immunology
Pubmed
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01/11/2017 11:29
Last modification date
20/08/2019 16:29