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http://purl.uniprot.org/citations/27522155http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27522155http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27522155http://www.w3.org/2000/01/rdf-schema#comment"

Background

Signaling through the T-cell receptor (TCR) is critical for T-cell development and function. Linker for activation of T cells (LAT) is a transmembrane adaptor signaling molecule that is part of the TCR complex and essential for T-cell development, as demonstrated by LAT-deficient mice, which show a complete lack of peripheral T cells.

Objective

We describe a pedigree affected by a severe combined immunodeficiency phenotype with absent T cells and normal B-cell and natural killer cell numbers. A novel homozygous frameshift mutation in the gene encoding for LAT was identified in this kindred.

Methods

Genetic, molecular, and functional analyses were used to identify and characterize the LAT defect. Clinical and immunologic analysis of patients was also performed and reported.

Results

Homozygosity mapping was used to identify potential defective genes. Sanger sequencing of the LAT gene showed a mutation that resulted in a premature stop codon and protein truncation leading to complete loss of function and loss of expression of LAT in the affected family members. We also demonstrate loss of LAT expression and lack of TCR signaling restoration in LAT-deficient cell lines reconstituted with a synthetic LAT gene bearing this severe combined immunodeficiency mutation.

Conclusion

For the first time, the results of this study show that inherited LAT deficiency should be considered in patients with combined immunodeficiency with T-cell abnormalities."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.org/dc/terms/identifier"doi:10.1016/j.jaci.2016.05.036"xsd:string
http://purl.uniprot.org/citations/27522155http://purl.org/dc/terms/identifier"doi:10.1016/j.jaci.2016.05.036"xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Kleta R."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Kleta R."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Stanescu H.C."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Stanescu H.C."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Beales P.L."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Beales P.L."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Adams S."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Adams S."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Woods C.G."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Woods C.G."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Bacchelli C."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Bacchelli C."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Gaspar H.B."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Gaspar H.B."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Qasim W."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Qasim W."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Nicholas A.K."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Nicholas A.K."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Pearce K."xsd:string
http://purl.uniprot.org/citations/27522155http://purl.uniprot.org/core/author"Pearce K."xsd:string
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