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
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
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DOI：
10.1086/301706
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发表时间：
1998-02-01
影响因子：
9.8
通讯作者：
Taylor, AMR
中科院分区：
文献类型：
--
作者：
Stankovic, T;Kidd, AMJ;Taylor, AMR
我们报告了在不列颠群岛的共济失调-毛细血管扩张（A-T）患者中观察到的59个ATM突变谱。在不列颠群岛原生家族中发现的51个ATM突变中，2个是创始突变，这11个突变中有2个在小脑变性和细胞特征方面具有较轻的临床表型。我们报道，在两个a - t家族中，一个ATM突变（7271T - >g）可能与纯合子和杂合子的乳腺癌风险增加有关（相对风险12.7;P = 0.0025），尽管在小脑变性程度方面存在较轻的a - t表型。这种突变（7271T -> G）也允许全长ATM蛋白的表达，其水平与未受影响的个体相当。此外，我们还研究了来自15个家庭的18例A-T患者，他们大多在儿童时期患上了白血病、淋巴瘤、白血病前期t细胞增殖或霍奇金淋巴瘤。在这些患者中发现了各种各样的ATM突变类型，包括错义突变和帧内缺失。我们还发现，25%的A-T患者携带框内缺失或错义突变，其中许多也与突变的ATM蛋白表达有关。
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, II 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.