中文摘要：

目的 对1例临床拟诊为神经纤维瘤Ⅰ型（neurofibromatosis type 1,NF-1）患者进行致病基因突变研究.方法 通过探针杂交富集患者神经纤维蛋白1 （neurofibromin 1,NF1）基因的全部编码区外显子及其旁侧序列进行高通量测序确定可疑突变,并用Sanger测序法对核心家系成员的相应目标基因区域进行测序验证.结果 在患者NF1基因的第8外显子检出一插入/缺失型突变（indel）c.789790delAGinsT（p.K263Nfs＊ 18）,造成突变点后的三联密码子阅读框发生改变而导致蛋白质翻译的提前终止.其表型正常父母均无此改变.在患者突变点下游第8内含子中还检出两个源自父亲的杂合多态性改变c.888＋ 108C＞T（rs2953000）和c.888＋ 118G＞T（rs2952999）,Sanger测序峰图显示这三处改变位于同一染色体.结论 c.789_790delAGinsT为来自父源的新生突变,确定为患者的致病原因,从而肯定临床诊断.该突变类型补充了NF1基因的突变数据库.比较Sanger测序技术,目标区域二代测序进行NF1基因突变检测,更为快捷、价廉和高效,适用于临床.

英文摘要：

Objective To identify the genetic etiology in a Chinese patient with neurofibromatosis type 1 （NF-1）.Methods All coding exons and the flanking sequences of neurofibromin 1 （NF1）gene from the patient were captured,individually barcoded and subjected to HiSeq2000 high-throughput sequencing.Suspected mutation was validated in the nuclear family members with Sanger sequencing.Results A novel indel mutation,c.789_790delAGinsT,was identified in the exon 8 of the NF1 gene in the patient but not in her asymptomatic parents.The mutation was predicted to have caused shifting of the reading frame and a premature downstream stop codon （p.K263Nfs ＊ 18）.Two known polymorphisms,c.888 ＋ 108 C〉 T （rs2953000） and c.888 ＋118 G〉T （rs2952999）,was detected in the flanking of the indel mutation in the patient and her father.Sequencing chromatogram for the family indicates that above changes are located on the same chromosome.Conclusion The c.789_790delAGinsT,as a de novo mutation occurring on the paternally derived chromosome,is most likely to be causative for the disease.Compared with Sanger sequencing,targeted next-generation sequencing is more efficient and can dramatically reduce the cost for the genetic testing of NF-1.