Ataxia-telangiectasia - A primary immunodeficiency revisited

The range of abnormalities seen in ataxia-telangiectasia can be accounted for, at least in part, by the failure of cells to process inevitable breaks in DNA correctly. ATM acts as a hierarchical kinase, with numerous potential substrates and downstream consequences. Possibly because of the stochastic way in which immune cells mature by gene rearrangements in the TCR and B-cell receptor (BCR) gene complexes, followed by negative selection (i.e., apoptosis) and then recruitment (i.e., replication) of appropriate cells, it could be anticipated that the immune status from one patient to the next would be variable-even between siblings sharing an identical mutation. If gene rearrangements occur in any other cell lineages, these also would contribute to the complex phenotype.