Ataxia Telangiectasia and Its Overlap with Nijmegen Breakage Syndrome and Ataxia-Like Disorders

Ataxia Telangiectasia (AT), Nijmegen Breakage Syndrome (NBS) and AT-Like Disorder (ATLD) are three closely related human diseases. AT, NBS and ATLD share several promi­nent cellular phenotypes including increased sensitivity to ionizing radiation, abnormal cell-cycle checkpoints, chromosome instability, immunodeficiency and accelerated shortening of telomeres. However, notable distinctions amongst AT, NBS and ATLD patients are also prevalent. W hile AT patients are defective in the ATM gene, ATLD and NBS patients have mutations in genes encoding an MRN protein complex consisting of M rel 1 (mutated in ATLD), Rad50 and Nbsl (mutated in NBS). The MRN complex plays critical and complicated roles in regulating ATM functions which, upon examination, justifies the similarities and distinctions between AT, NBS and ATLD patients. Continued research and investigation into the mechanisms and pathways involved in MRN and ATM signaling will facilitate advanced diagnosis and treatment of AT and related diseases.