Founder effects for ATM gene mutations in Italian Ataxia Telangiectasia families

Ann Hum Genet. 2009 Sep;73(Pt 5):532-9. doi: 10.1111/j.1469-1809.2009.00535.x.


We screened ATM gene mutations in 104 Italian Ataxia-Telangiectasia patients from 91 unrelated families (detection rate 90%) and found 21 recurrent mutations in 63 families. The majority (67%) of patients were compound heterozygotes, while 33% were homozygotes. To determine the existence of common haplotypes and potential founder effects, we analyzed five microsatellite markers within and flanking the ATM gene. Haplotype analysis was carried out in 48/63 families harbouring 16 of the 21 recurrent mutations. Forty different haplotypes were detected in the 48 A-T families studied. We found that the majority of patients with the same recurrent mutation originated from the same geographical area. All but one recurrent mutation analyzed displayed a common haplotype suggesting a single origin that then spread to different geographical areas. The high number of different haplotypes does not allow the screening of ATM mutations by haplotype analysis alone in the Italian population. The finding of recurrent public mutations without founder effect suggests the existence of 'mild' hot spots of mutation located along the sequence of the ATM gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxia Telangiectasia / genetics*
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / genetics*
  • Cells, Cultured
  • DNA-Binding Proteins / genetics*
  • Female
  • Founder Effect*
  • Haplotypes
  • Humans
  • Italy
  • Male
  • Mutation*
  • Pedigree
  • Protein Serine-Threonine Kinases / genetics*
  • Tumor Suppressor Proteins / genetics*


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