三例散发Ⅰ型神经纤维瘤病NF1基因突变检测

Detection of NF1 gene mutation in three patients with neurofibromatosis type 1

目的:对3例Ⅰ型神经纤维瘤病(neurofibromatosis type1,NF1)患者及其家系进行致病基因突变检测。方法:应用目标序列捕获高通量测序技术对3例Ⅰ型神经纤维瘤病患者进行测序。患者检测出可疑突变类型后,应用多重连接探针扩增技术(multiplex ligation-dependent probe amplification,MLPA)及Sanger测序技术对患者及其家系成员进行突变位点验证。并采用SIFT、PolyPhen_2、Mutation Taster和GERP++软件对致病性不明的位点进行致病性预测。结果:3例Ⅰ型神经纤维瘤病患者分别检测到1个NF1基因变异:NF1基因整体杂合缺失、c.4064delC和Exon14_36del。其中c.4064delC与Exon14_36del未见文献报道,为新发突变。结论:本研究中3例Ⅰ型神经纤维瘤病患者中发现3个NF1基因突变,其中2个为新发突变,扩充了NF1基因突变位点。

Objective:To detect the mutation of NF1 gene in three sporadic patients with neurofibromatosis type1(NF1).Methods:Target sequence capture high-throughput sequencing technology was performed in three patients with NF1.After the pathogenic genotypes confirmed,the mutation was verified by multiplex ligation-dependent probe amplification analysis or Sanger sequencing method.SIFT,PolyPhen_2,Mutation Taster and GERP++software were used to predict the effect of the mutation on protein function.Results:Three different mutations:gross NF1 gene deletions,c.4064delC and exon14_36del of NF1 gene were identified in the three patients respectively.The c.4064delC and exon14_36del have not been reported previously.Conclusion:Three mutations in NF1 gene were identified in these patients.Two of those mutations were novel,which broaden the spectrum of NF1 mutations.