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Molecular pathology of ataxia telangiectasia

CR-UK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK

Correspondence to:
Professor A M R Taylor
CR-UK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK;A.M.R.Taylor{at}bham.ac.uk
ABSTRACT
Ataxia telangiectasia (A-T) is one of a group of autosomal recessive cerebellar ataxias. Presentation is usually by the age of 2 years and ataxia of both upper and lower limbs develops, such that by early teenage most patients require a wheelchair for mobility. Speech and eye movement are also affected. Other important features are t(7;14) translocations, immunodeficiency, a high serum  fetoprotein concentration, growth retardation, telangiectasia—most noticeably on the bulbar conjunctiva—and a very high risk of developing a lymphoid tumour. Patients also show an increased sensitivity to ionising radiation. The classic form of A-T results from the presence of two truncating ATM mutations, leading to total loss of the ATM protein, a protein kinase. Importantly, A-T shows clinical heterogeneity, including milder forms where neurological progression may be slower or of later onset. In these cases there is a correlation between the preservation of neurological function, decreased radiosensitivity, and the degree of retained ATM protein kinase activity. Considerable scope remains for understanding the progress of the disorder in relation to the types of ATM mutation present.

Abbreviations: AFP, fetoprotein; A-T, ataxia telangiectasia; ATLD, ataxia telangiectasia-like disorder; AOA, ataxia oculomotor apraxia; IR, ionising radiation; NBS, Nijmegen breakage syndrome; SCAN1, spinocerebellar ataxia with axonal neuropathy

Keywords: molecular pathology; ataxia telangiectasia; immunodeficiency; cancer prevalence

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