title: New mutations, polymorphisms, and rare variants in the ATM gene detected by a novel SSCP strategy.
abstract: The gene for ataxia-telangiectasia, ATM, spans about 150 kb of genomic DNA. ATM mutations are found along the entire gene, with no evidence of a mutational hot spot. Using DNA as the starting material, we screened the ATM gene in 92 A-T patients, using an optimized single-strand conformation polymorphism (SSCP) technique that detected all previously known mutations in the polymerase chain reaction (PCR) segments being analyzed. To expedite screening, we sequentially loaded the SSCP gels with three different sets of PCR products that were pretested to avoid overlapping patterns. Many of the DNA changes we detected were intragenic polymorphisms. Of an expected 177 unknown mutations, we detected approximately 70%, mostly protein truncating mutations (that would have been detectable by protein truncation testing if RNA starting material had been available). Mutations have now been defined for every exon of the ATM gene. Herein, we present 35 new mutations and 34 new intragenic polymorphisms or rare variants within the ATM gene. This is the most comprehensive compilation of ATM polymorphisms assembled to date. Defining polymorphic sites as well as mutations in the ATM gene will be of great importance in designing automated methods for detecting mutations.
authors.affiliation: Department of Pathology, School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1732, USA.
authors.forename: S
authors.initials: S
authors.lastname: Castellví-Bel
authors.forename: S
authors.initials: S
authors.lastname: Sheikhavandi
authors.forename: M
authors.initials: M
authors.lastname: Telatar
authors.forename: L Q
authors.initials: LQ
authors.lastname: Tai
authors.forename: M
authors.initials: M
authors.lastname: Hwang
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.forename: R
authors.initials: R
authors.lastname: Cheng
authors.forename: R A
authors.initials: RA
authors.lastname: Gatti
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins; D005006:Ethnicity / Q000235:genetics; D005091:Exons / Q000235:genetics; D005821:Genetic Techniques; D006801:Humans; D009154:Mutation; D010443:Peptide Chain Termination, Translational / Q000235:genetics; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics*; D025521:Tumor Suppressor Proteins; D014481:United States
chemical_list: D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases