Ataxia-telangiectasia - A primary immunodeficiency revisited

The range of abnormalities seen in ataxia-telangiectasia can be accounted f or, at least in part, by the failure of cells to process inevitable breaks in DNA correctly. ATM acts as a hierarchical kinase, with numerous potentia l substrates and downstream consequences. Possibly because of the stochasti c 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., a poptosis) and then recruitment (i.e., replication) of appropriate cells, it could be anticipated that the immune status from one patient to the next w ould be variable-even between siblings sharing an identical mutation. If ge ne rearrangements occur in any other cell lineages, these also would contri bute to the complex phenotype.