Ataxia-telangiectasia: an interdisciplinary approach to pathogenesis.
Ataxia-telangiectasia is a syndrome with many facets, involving a progressive cerebellar ataxia, immunodeficiency, cancer susceptibility, radiosensitivity, defects in DNA repair/processing, chromosomal breakage and rearrangements, elevated serum alphafetoprotein, and premature aging. Ataxia-telangiectasia is an autosomal recessive disorder, rare in outbred populations; carriers of the ataxia-telangiectasia gene may be as common as 1 in 60 and have subclinical radiosensitivity and cancer susceptibility. One estimate suggests that 8.8% of patients with breast cancer could be carriers of ataxia-telangiectasia. These carriers may be responsible for underestimating normal tolerance doses for radiation therapy by 15% to 20%; thus by preselecting and excluding carriers of ataxia-telangiectasia from cohorts of patients with cancer, conventional radiation doses might be increased so as to improve greatly the efficacy of radiotherapy. The genes for the 3 most common ataxia-telangiectasia complementation groups, which include 97% of tested families, have recently been localized to the long arm of chromosome 11.
Gatti
R A
RA
Department of Pathology, UCLA School of Medicine 90024.
Boder
E
E
Vinters
H V
HV
Sparkes
R S
RS
Norman
A
A
Lange
K
K
D001260:Ataxia Telangiectasia / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D001921:Brain / Q000473:pathology; D002874:Chromosome Mapping; D008040:Genetic Linkage; D006801:Humans; D011836:Radiation Tolerance