Multiple sclerosis in a radiosensitive family with low levels of the ATM protein

Australas Radiol. 2002 Sep;46(3):267-74. doi: 10.1046/j.1440-1673.2002.01058.x.

Abstract

Multiple sclerosis (MS) is a chronic neurological disease of the central nervous system (CNS) characterized by demyelination associated with progressive disability. The mechanisms underlying the pathogenesis of MS remain a mystery. The highly pleiotropic syndrome known as ataxia telangiectasia (A-T) overlaps with MS in that it also presents with demyelination in the CNS. Whether demyelination in MS or in A-T is initiated through neuronal degeneration or immune dysfunction is not yet known. However, unlike MS, the underlying cause of A-T is known to result from mutations in the A-T gene (ATM) that often result in the complete loss of ATM protein and loss/gain of function. ATM is implicated in neurological degeneration, particularly in the cerebellum, cellular apoptosis, immunodeficiency, double stranded deoxyribonucleic acid (DNA) rejoining, VDJ antibody recombination, tumour suppression, particularly T-lymphoid malignancies, signal transduction, cell-cycle control and cellular radiohypersensitivity. In this study, we describe a case of MS in a family with cellular radiosensitivity and abnormally low postinduction levels of the ATM protein. Defective DNA repair/rejoining may impact on autoimmunity.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Ataxia Telangiectasia / genetics
  • Ataxia Telangiectasia Mutated Proteins
  • Autoimmunity
  • Biopsy
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Humans
  • Male
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / metabolism
  • Pedigree
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Radiation Tolerance*
  • Skin / metabolism
  • Skin / pathology
  • Tumor Suppressor Proteins

Substances

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