Adult-onset ataxia telangiectasia due to ATM 5762ins137 mutation homozygosity

Ann Neurol. 2004 Jun;55(6):891-5. doi: 10.1002/ana.20139.

Abstract

Ataxia telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder that arises because of mutations in the ATM gene. The 5762ins137 A-->G point mutation activates a cryptic splice donor site resulting in a 137 bp intronic insert being aberrantly spliced into the ATM transcript. However, normal ATM transcript also is produced from this affected allele, albeit at significantly reduced levels. An exceptionally mild A-T phenotype occurs as a result of homozygosity for the 5762ins137 mutation because of relative preservation of ATM protein expression/kinase activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine / genetics
  • Ataxia Telangiectasia / genetics*
  • Ataxia Telangiectasia / metabolism
  • Ataxia Telangiectasia / pathology
  • Ataxia Telangiectasia Mutated Proteins
  • Blood Cells / metabolism
  • Blood Cells / radiation effects
  • Blotting, Western / methods
  • Cell Cycle Proteins
  • Cell Line
  • Cerebellum / pathology
  • DNA Mutational Analysis
  • DNA-Binding Proteins
  • Glycine / genetics
  • Homozygote*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Phosphorylation
  • Point Mutation*
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA Splice Sites
  • Radiation Tolerance / genetics
  • Serine
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • RNA Splice Sites
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Serine
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases
  • Alanine
  • Glycine