PDF(Pubmed)
Abstract：
Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by progressive ataxia, choreoathetosis and immunodeficiency beginning in early childhood. An 8-year-old girl was referred with a diagnosis of AT. She had gait disturbance and dysarthria for 3years. Multiple cutaneous telangiectases were observed on her face, trunk and limbs. Sequence analysis of the ATM gene revealed a homozygous c.7308-15A>G mutation in IVS49. Human Splicing Finder predicted that the mutation could activate an intronic cryptic acceptor site. We designed primers for amplification of related exons (48-50) from cDNA for evaluating splicing pattern. Sequencing of ATM exons 48-50 revealed a 14-nucleotide insertion from intron 49, between exons 49 and 50, resulting in premature termination of translation at codon 2439. To conclude, we report a novel mutation in a classical AT case, which resulted in an alternatively spliced transcript and was predicted to form a truncated protein or null protein due to nonsense-mediated decay.
摘要：
共济失调-毛细血管扩张症（AT）是一种常染色体隐性遗传疾病，以进行性共济失调为特征，舞蹈症和免疫缺陷始于儿童早期。一名8岁女孩被诊断为AT。她有步态障碍和构音障碍3年。在她的脸上观察到多处皮肤毛细血管扩张,躯干和四肢.ATM基因的序列分析揭示了IVS49中的纯合c.7308-15A>G突变。人类剪接Finder预测该突变可以激活内含子隐蔽受体位点。我们设计了从cDNA中扩增相关外显子（48-50）的引物，以评估剪接模式。ATM外显子48-50的测序揭示了在外显子49和50之间从内含子49插入14个核苷酸,导致在密码子2439处翻译的提前终止。最后，我们在一个经典的AT病例中报告了一个新的突变，导致选择性剪接的转录物，并预测由于无义介导的衰变而形成截短的蛋白质或无效蛋白质。
