Ataxia-telangiectasia: identification and detection of founder-effect mutations in the ATM gene in ethnic populations

Am J Hum Genet. 1998 Jan;62(1):86-97. doi: 10.1086/301673.


To facilitate the evaluation of ATM heterozygotes for susceptibility to other diseases, such as breast cancer, we have attempted to define the most common mutations and their frequencies in ataxia-telangiectasia (A-T) homozygotes from 10 ethnic populations. Both genomic mutations and their effects on cDNA were characterized. Protein-truncation testing of the entire ATM cDNA detected 92 (66%) truncating mutations in 140 mutant alleles screened. The haplotyping of patients with identical mutations indicates that almost all of these represent common ancestry and that very few spontaneously recurring ATM mutations exist. Assays requiring minimal amounts of genomic DNA were designed to allow rapid screening for common ethnic mutations. These rapid assays detected mutations in 76% of Costa Rican patients (3), 50% of Norwegian patients (1), 25% of Polish patients (4), and 14% of Italian patients (1), as well as in patients of Amish/Mennonite and Irish English backgrounds. Additional mutations were observed in Japanese, Utah Mormon, and African American patients. These assays should facilitate screening for A-T heterozygotes in the populations studied.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Ataxia Telangiectasia / ethnology*
  • Ataxia Telangiectasia / genetics*
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • DNA Mutational Analysis
  • DNA, Complementary / analysis
  • DNA-Binding Proteins
  • Ethnicity / genetics
  • Female
  • Haplotypes
  • Heterozygote
  • Humans
  • Male
  • Mutation*
  • Protein Serine-Threonine Kinases*
  • Proteins / genetics*
  • RNA / analysis
  • Racial Groups / genetics
  • Tumor Suppressor Proteins


  • Cell Cycle Proteins
  • DNA, Complementary
  • DNA-Binding Proteins
  • Proteins
  • Tumor Suppressor Proteins
  • RNA
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases