New gene defect for SCID identified


Published Online: July 14, 2016

Severe combined immunodeficiency or SCID is one of the most devastating immunological conditions. Babies are born without functional immune systems, especially low T cell numbers, and as a result are vulnerable to many different pathogens. Without effective treatment, most infants will die in the first year of life. SCID can arise from a number of gene defects and with the advances in gene identification technology, novel genes leading to SCID are being identified.

In a recent article by Bacchelli and colleagues studied 5 infants from a consanguineous family who presented with SCID. Patients had presented with severe and recurrent infections and all had low T cell numbers although B and NK cell numbers were relatively normal. Gene mapping technology from family members identified a region on chromosome 16 where the defective gene might be located. The investigators then sequenced candidate genes in this region and in affected patients identified mutations in the gene for LAT (Linker for activation of T cells).

LAT is known to be a molecule involved in coordinating signals downstream of the T cell receptor and plays a critical role in processing signals that allow T cells to develop in the thymus. Mice with mutations in LAT lack T cells but this is the first time that mutations in LAT have been described in humans. The investigators also conducted a series of investigations on the effect of the gene mutation on the protein. They showed that the mutation results in absent LAT protein expression and that in a LAT deficient cell line, expressing the mutant gene is not able to restore LAT specific functions, whereas these functions are restored by expressing wild type LAT.

This study has clinical implications in that it identifies another gene that can cause SCID and so LAT should be added to the panel of genes that SCID patients should be screened for. The study also highlights the importance of the LAT gene and protein in human T cell development.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

Close-up of pine tree branches in Winter Close-up of pine tree branches in Winter