Genetic mutation identified for novel form of severe combined immunodeficiency

Research led by BRC Deputy Director Professor Bobby Gaspar and supported by the BRC-funded GOSgene facility, has found that a mutation in the linker for activation of T-cells (LAT) gene leads to a specific form of severe combined immunodeficiency (SCID).SCIDs are a group of immunological disorders characterised by a lack of lymphocyte development and function, and more specifically, a low number of autologous T-cells. Untreated patients with SCID do not survive past the first year of life.

T-cell receptor (TCR) signalling is an essential process for the development of T-cells and currently a number of genetic defects in the TCR signalling pathway have been shown to lead to a SCID. LAT performs a critical function in TCR signal transduction and LAT has been considered a strong candidate for SCID.

In this study, genetic, molecular and functional analyses were used to identify and characterise the LAT defect in five patients with a well-defined SCID immunophenotype, these patients demonstrated a significant lack of T-cells, caused by a frameshift mutation in LAT.

In these patients, there was a mutation in the LAT gene which led to a complete loss of LAT expression and function, suggesting that inherited LAT deficiency should be considered in patients with combined immunodeficiency with T-cell abnormalities.

These findings were published in Journal of Allergy and Clinical Immunology.