The ataxia-telangiectasia mutated (ATM) gene, which is mutated in the autosomal recessive disorder ataxia-telangiectasia (AT), was isolated in 1995 by positional cloning. Although in vitro cell fusion studies had suggested that AT was genetically heterogeneous, all AT patients studied to date have been found to harbor mutations in the ATM gene. More that 100 ATM mutations occurring in AT patients have been documented. The mutations are broadly distributed throughout the ATM gene. Except for patients from families with known consanguinity, most AT patients are compound heterozygotes. The majority (> 70%) of mutations are predicted to lead to protein truncation. A significant number of the reported mutations affect mRNA splicing with at least half of the coding exons (32/62) having been observed to undergo exon skipping. The large size of the ATM gene, 66 exons spanning approximately 150 kb of genomic DNA, together with the diversity and broad distribution of mutations in AT patients greatly limits the utility of direct mutation screening as a diagnostic tool, or method of carrier identification, except where founder effect mutations are involved.