Australas Radiol 2002 Sep;46(3):267-274
Clarke RA, Fang ZM, Lee CS, Sarris M, Murrell D, Kearsley JH.
Division of Cancer Services, The St George Hospital, University of New South Wales, Australia Department of Dermatology, The St George Hospital, University of New South Wales, Australia Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney University, Sydney, Australia.
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.