Improved diagnostic testing for ataxia-telangiectasia by immunoblotting of nuclear lysates for ATM protein expression

Mol Genet Metab. 2003 Dec;80(4):437-43. doi: 10.1016/j.ymgme.2003.09.008.


The laboratory diagnosis of ataxia-telangiectasia (A-T) currently relies upon measurement of serum alphafetoprotein (AFP) and cellular sensitivity to ionizing radiation. A previous report suggests that immunoblotting of whole cell lysates from lymphoblastoid cell lines (LCLs) might be informative for diagnosis. To further evaluate this possibility, and improve sensitivity, we performed immunoblotting for ATM protein on nuclear lysates of 71 consecutive radiosensitive LCLs that were established from patients with clinical features suggestive of A-T. Fifty-two LCLs (73%) contained no detectable ATM protein, with a representative sample (N=25) testing negative for ATM kinase activity, having at least one ATM mutation, and having elevated AFP levels; these results confirmed the diagnosis. Seventeen LCLs (24%) expressed intermediate or normal levels of ATM protein and exhibited normal ATM kinase activity; follow-up studies failed to detect ATM mutations and AFP levels were normal in all but three. Of the remaining two radiosensitive LCLs, one had 35% of normal protein with normal kinase activity and no ATM mutations. The other LCL had 9% of normal protein, with intermediate levels of kinase activity, a homozygous missense ATM mutation, and elevated AFP. Our data suggest that it is very uncommon to encounter bonafide A-T patients with more than trace amounts of ATM protein. We conclude that immunoblotting for ATM protein is of higher specificity for diagnosing A-T than radiosensitivity testing. In addition, we have documented in vitro radiosensitivity in other patients who share some clinical features with A-T.

Publication types

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

MeSH terms

  • Ataxia Telangiectasia / diagnosis*
  • Ataxia Telangiectasia / genetics
  • Ataxia Telangiectasia / pathology
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • Cell Line
  • Cell Nucleus / metabolism
  • Child, Preschool
  • DNA-Binding Proteins
  • Heterozygote
  • Humans
  • Immunoblotting / methods*
  • Lymphocytes / metabolism
  • Lymphocytes / radiation effects
  • Protein Serine-Threonine Kinases / analysis*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Radiation Tolerance
  • Sensitivity and Specificity
  • Tumor Suppressor Proteins


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