title: DHPLC screening of ATM gene in Italian patients affected by ataxia-telangiectasia: fourteen novel ATM mutations.
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.
authors.affiliation: IRCCS-CSS Mendel Institute, Rome, Italy.
authors.forename: Monia
authors.initials: M
authors.lastname: Magliozzi
authors.forename: Maria
authors.initials: M
authors.lastname: Piane
authors.forename: Isabella
authors.initials: I
authors.lastname: Torrente
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Sinibaldi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rizzo
authors.forename: Camilla
authors.initials: C
authors.lastname: Savio
authors.forename: Patrizia
authors.initials: P
authors.lastname: Lulli
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Luca
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Luciana
authors.initials: L
authors.lastname: Chessa
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases