Genetic complementation analysis of ataxia telangiectasia and Nijmegen breakage syndrome: a survey of 50 patients.
Genetic complementation analysis of ataxia telangiectasia and Nijmegen breakage syndrome: a survey of 50 patients.
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共济失调毛细血管扩张症和奈梅亨断裂综合征的基因互补分析：50 例患者的调查。
DOI：
10.1159/000132673
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
D. Bootsma
中科院分区：
文献类型：
--
作者：
N. Jaspers;R. Gatti;C. Baan;P. Linssen;D. Bootsma
来自失调性毛细血管扩张（AT）或奈梅亨断裂综合征（NBS）患者的培养细胞对电离辐射敏感。辐射暴露后，DNA复制速率受到的抑制程度低于正常细胞，而染色体畸变的频率则增加。这两种特征都已用于对有限系列患者的基因互补研究。在这里，我们报告了对来自不同来源的50名患者的成纤维细胞株进行扩展互补研究的结果，使用耐辐射DNA复制特性作为标记。鉴定出6个不同的基因互补组。其中，AB、C、D、E四种（其中AB最大）代表有AT临床症状的患者。NBS患者分为V1和V2两组。V2组有1例同时出现AT和NBS临床症状，提示两种疾病密切相关。在AT中，任何关于临床特征或种族起源的群体特异性模式都不明显。除了放射敏感型ATs外，还存在另一类患者，其特点是临床病程相对较轻，放射敏感性较弱。结论是，至少六种不同基因中的一种缺陷可能是人类遗传放射敏感性的基础。为了促进对已定义缺陷的研究，提出了一份完整的基因特征成纤维细胞菌株清单。
Cultured cells from patients with ataxia telangiectasia (AT) or Nijmegen breakage syndrome (NBS) are hypersensitive to ionizing radiation. After radiation exposure, the rate of DNA replication is inhibited to a lesser extent than in normal cells, whereas the frequency of chromosomal aberrations is enhanced. Both of these features have been used in genetic complementation studies on a limited series of patients. Here we report the results of extended complementation studies on fibroblast strains from 50 patients from widely different origins, using the radioresistant DNA replication characteristic as a marker. Six different genetic complementation groups were identified. Four of these, called AB, C, D, and E (of which AB is the largest), represent patients with clinical signs of AT. Patients having NBS fall into two groups, V1 and V2. An individual with clinical symptoms of both AT and NBS was found in group V2, indicating that the two disorders are closely related. In AT, any group-specific patterns with respect to clinical characteristics or ethnic origin were not apparent. In addition to the radiosensitive ATs, a separate category of patients exists, characterized by a relatively mild clinical course and weak radiosensitivity. It is concluded that a defect in one of at least six different genes may underlie inherited radiosensitivity in humans. To facilitate research on defined defects, a complete list of genetically characterized fibroblast strains is presented.