Ataxia-telangiectasia: mutations in ATM cDNA detected by protein-truncation screening

Am J Hum Genet. 1996 Jul;59(1):40-4.


We have examined the distal half of the ataxia-telangiectasia (A-T) gene transcript for truncation mutations in 48 A-T affecteds. We found 21 mutations; 4 of the mutations were seen in more than one individual. Genotyping of the individuals sharing mutations, by using nearby microsatellite markers, established that three of the four groups shared common haplotypes, indicating that these were probably founder effects, not public mutations. The one public mutation was found in two American families, one of Ashkenazi Jewish background and the other not. Most truncations deleted the PI3-kinase domain, although some exceptions to this were found in patients with typical A-T phenotypes. All patients not previously known to be consanguineous were found to be compound heterozygotes when mutations could be identified--that is, normal and abnormal protein segments were seen on SDS-PAGE gels. All 48 patients gave RT-PCR products, indicating the presence of relatively stable mRNAs despite their mutations. These results suggest that few public mutations or hot spots can be expected in the A-T gene and that epidemiological studies of A-T carrier status and associated health risks will have to be designed around populations with frequent founder-effect mutations, despite the obvious limitations of this approach.

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 / diagnosis
  • Ataxia Telangiectasia / genetics*
  • Ataxia Telangiectasia Mutated Proteins
  • Base Sequence
  • Cell Cycle Proteins
  • Consanguinity
  • DNA Mutational Analysis
  • DNA Primers / genetics
  • DNA, Complementary / genetics*
  • DNA-Binding Proteins
  • Ethnicity / genetics
  • Female
  • Founder Effect
  • Genetic Techniques
  • Heterozygote
  • Humans
  • Male
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Protein Serine-Threonine Kinases*
  • Proteins / genetics*
  • Sequence Deletion
  • Tumor Suppressor Proteins


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