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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1998 Feb;62(2):334–345. doi: 10.1086/301706

ATM mutations and phenotypes in ataxia-telangiectasia families in the British Isles: expression of mutant ATM and the risk of leukemia, lymphoma, and breast cancer.

T Stankovic 1, A M Kidd 1, A Sutcliffe 1, G M McGuire 1, P Robinson 1, P Weber 1, T Bedenham 1, A R Bradwell 1, D F Easton 1, G G Lennox 1, N Haites 1, P J Byrd 1, A M Taylor 1
PMCID: PMC1376883  PMID: 9463314

Abstract

We report the spectrum of 59 ATM mutations observed in ataxia-telangiectasia (A-T) patients in the British Isles. Of 51 ATM mutations identified in families native to the British Isles, 11 were founder mutations, and 2 of these 11 conferred a milder clinical phenotype with respect to both cerebellar degeneration and cellular features. We report, in two A-T families, an ATM mutation (7271T-->G) that may be associated with an increased risk of breast cancer in both homozygotes and heterozygotes (relative risk 12.7; P=. 0025), although there is a less severe A-T phenotype in terms of the degree of cerebellar degeneration. This mutation (7271T-->G) also allows expression of full-length ATM protein at a level comparable with that in unaffected individuals. In addition, we have studied 18 A-T patients, in 15 families, who developed leukemia, lymphoma, preleukemic T-cell proliferation, or Hodgkin lymphoma, mostly in childhood. A wide variety of ATM mutation types, including missense mutations and in-frame deletions, were seen in these patients. We also show that 25% of all A-T patients carried in-frame deletions or missense mutations, many of which were also associated with expression of mutant ATM protein.

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Selected References

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