Abstract: The gene for ataxia-telangiectasia (A-T:MIM: #208900), ATM,
spans about 150~kb of genomic DNA and is composed of 62 coding exons. ATM
mutations are found along the entire coding sequence of the gene, without
evidence of mutational hot spots. Using DNA as the starting material, we used
denaturing high performance liquid chromatography (DHPLC) technique to search
for ATM gene mutations. Initially, DHPLC was validated in a retrospective
study of 16 positive control samples that included 19 known mutations; 100%
of mutations were detected. Subsequently, DHPLC was used to screen for
mutations a cohort of 22 patients with the classical form of A-T. A total of 27
different mutations were identified on 38 of the 44 alleles, corresponding to a
86% detection rate. Fourteen of the mutations were novel. In addition, 15
different variants and polymorphisms of unknown functional significance were
found. The high incidence of new and individual A-T mutations in our cohort of
patients demonstrates marked mutational heterogeneity of A-T in Italy and
corroborate the efficiency of DHPLC as a method for the mutation screening of
A-T patients.
