ATM mutations, haplotype analysis, and immunological status of Russian patients with ataxia telangiectasia.
ATM mutations, haplotype analysis, and immunological status of Russian patients with ataxia telangiectasia.
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DOI：
10.1002/humu.9341
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发表时间：
2005-06-01
期刊：
影响因子：
3.9
通讯作者：
Lavin, Martin F
中科院分区：
文献类型：
--
作者：
Birrell, Geoff W;Kneebone, Katherine;Lavin, Martin F
ATM 基因突变导致常染色体隐性遗传病——毛细血管扩张性共济失调 (A-T)。不同种族的突变分布在 66 个外显子 ATM 基因的整个长度上。在这项研究中，对来自 16 个俄罗斯家庭的 A-T 患者进行了免疫状态评估和 ATM 单倍型分析，并筛查了 ATM 突变。进行单倍型分析以提高突变检测的效率。在 32 个等位基因中的 19 个 (59%) 中发现了预计会导致疾病的突变，其中包括通过单倍型分析和突变筛查在 8/32 (25%) 个等位基因中发现的截短突变 (c.5932G>T)。在其他欧洲 A-T 群体中发现这种突变的丰度较低，表明这种创始人效应突变可能起源于俄罗斯。这种突变的丰富性可能允许对癌症患者进行大规模筛查，以帮助阐明 ATM 在乳腺癌和其他癌症中的作用。其余的九个突变以前未被报道，并且增加了在整个基因中发现的众多独特突变。
Mutations in the ATM gene are responsible for the autosomal recessive disorder, ataxia telangiectasia (A-T). Mutations in different ethnic groups are distributed along the entire length of the large, 66 exon ATM gene. In this study, A-T patients from 16 Russian families were assessed for immunological status and ATM haplotype analysis, and screened for ATM mutations. Haplotype analysis was performed to enhance the efficiency of mutation detection. Mutations predicted to cause disease were identified in 19 of 32 alleles (59%), including a truncating mutation (c.5932G>T) that was identified in 8/32 (25%) alleles both by haplotype analysis and mutation screening. This mutation has been found in low abundance in other European A-T cohorts suggesting that this founder-effect mutation may be of Russian origin. The abundance of this mutation may allow for large-scale screening of cancer patients to help clarify the role of ATM in breast and other cancers. Nine of the remaining mutations were previously unreported, and add to the multitude of unique mutations found throughout the gene.