Absence of mutations in ATM, the gene responsible for ataxia telangiectasia in patients with cerebellar ataxia

Ataxia-telangiectasia (AT) is an autosomal recessive multisystent disorder presenting in childhood with progressive cerebellar ataxia, oculocutaneous telangiectasia, immune deficiency, radiosensitivity, and cancer predisposit ion. The gene for AT, designated ATM (AT, mutated) encodes a protein with a carboxy-terminal phosphoinositide-3 kinase domain which is involved in cel l cycle checkpoints and other responses to genotoxic stress. Most of the pa tients with the classical AT phenotype are homozygous or compound heterozyg ous for severe mutations causing truncation or destabilization of the ATM p rotein. Patients with a milder forms of disease, called AT variants, have b een found to be either homozygous for milder mutations or compound heterozy gotes for null alleles and mild mutations. In order to define the clinical phenotype of patients homozygous (or compound heterozygotes) for other, mil der mutations, we decided to search for ATM mutations in patients with eith er sporadic or familial idiopathic ataxia. Thirty-four patients with idiopa thic cerebellar ataxia, aged 3-77 years, were screened for mutations in the ATM coding region. There were 12 familial cases. None of the patients had abnormal immunoglobulin or alpha-fetoprotein levels, and none had mutations in the ATM coding region. In this heterogeneous group of patients with cer ebellar ataxia we found no mutations in the ATM gene. We conclude that muta tions in the ATM gene are probably not a common cause for cerebellar ataxia other than AT.