中国人群Ⅰ型神经纤维瘤病基因分子特征及临床表型相关性研究

发布时间：2018-05-27 04:29

本文选题：Ⅰ型神经纤维瘤病 + 突变分析　；参考：《上海交通大学》2015年博士论文

【摘要】：目的:在109例疑似I型神经纤维瘤病(NF1)的中国病人中揭示NF1基因突变谱及基因型表型相关性,并且在中国大陆建立一种综合的有效检测NF1突变的策略。方法:我们用Sanger测序,多重连接探针扩增法(MLPA),结合c DNA测序筛查了100个家庭中109例疑似NF1的病人(咖啡斑,神经纤维瘤等)。结果:我们发现了97例有致病突变的患者,其中34个为新突变。结论:我们综合检测方法的总突变检出率为89%(89/100),在符合美国国立卫生研究院(NIH)诊断标准组为93%(70/75),构建了一个较大的中国人群NF1基因的突变谱。基于这些结果,将促使建立中国I型神经纤维病早期诊断和遗传咨询的最优策略。此外,我们的研究发现1)那些临床上只表现为多发咖啡斑的人有很大概率是NF1(76%)和一定概率(24%)是由于其他类似NF1的疾病;2)15号外显子是一个潜在的突变热点;3)Lisch结节对于NF1是一个非常可靠的诊断标准,尤其是对于6岁以上的患者;4)贫血痣是一个潜在的新诊断标准。
[Abstract]:Objective: to reveal the relationship between NF1 gene mutation and genotype phenotype in 109 Chinese patients with suspected type I neurofibromatosis (NF1), and to establish a comprehensive and effective strategy for detecting NF1 mutation in mainland China. Methods: Sanger sequencing, multiplex probe amplification and c DNA sequencing were used to screen 109 suspected NF1 patients (coffee-spot, neurofibroma, etc.) in 100 families. Results: we found 97 patients with pathogenic mutations, 34 of which were new mutations. Conclusion: the total mutation detection rate of our comprehensive detection method is 89% / 100%, and the mutation profile of NF1 gene in a large Chinese population is constructed in the diagnostic standard group of National Institutes of Health (NIH). Based on these results, an optimal strategy for early diagnosis and genetic counseling of type I neurofibropathy in China will be established. In addition, Our study found that (1) those who clinically only present with multiple coffee spots have a high probability of NF176) and a certain probability of 24% because of other diseases similar to NF1.) exon 15 is a potential mutation hot spot in the case of NF1. A very reliable diagnostic standard, Anaemic nevus is a potential new diagnostic criterion, especially for patients over 6 years of age.
【学位授予单位】：上海交通大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R596.1

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