三例散发I型神经纤维瘤病NF1基因突变检测

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。

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

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.