SPECULATIONS ON THE ATAXIA-TELANGIECTASIA DEFECT

Ataxia-telangiectasia (A-T) is inherited as an monogenetic autosomal recessive disease. Ataxia appears around I year of age and progresses until the patient becomes wheelchair-bound, usually by age 10. This progress correlates with deterioration of Purkinje cells in the cerebellum. Sinopulmonary infections are common in patients from some countries but not others. One-third of the patients develop a neoplasm, usually lymphoid, sometime during their shortened lives. Conventional doses of radiation therapy for such cancers are contraindicated since A-T patients are hypersensitive to ionizing radiation. Five complementation groups have been described, based on correction of radioresistant DNA synthesis of fused fibroblasts from pairs of patients. Chromosomal translocations are found in 5-10% of peripheral T cells from most patients and the translocation breakpoints involvolve sites of normal somatic DNA rearrangment. Thus, the A-T gene(s) effects several cell lineages, suggesting that it is a "housekeeping" gene. Other speculations on "candidate genes" are considered. Recent progress localizing A-T to chromosome 11q23 is reviewed. © 1991 Academic Press, Inc.