应用高通量测序技术检测一个Ⅰ型神经纤维瘤病家系基因突变

Detection of gene mutation in a pedigree with neurofibromatosis type 1 by high-throughput sequencing technology

目的对1个I型神经纤维瘤病家系进行基因突变检测,为该家系成员提供遗传咨询并指导产前诊断。方法利用目标基因捕获和新一代高通量测序技术,对家系内1名症状典型患者N F 1基因编码区及其临近序列进行突变检测,对发现的可疑位点进行Sanger测序验证,并在家系内成员中验证所检测到的变异是否在家系内共分离。结果在该家系中,发现N F 1基因第18外显子存在一个微小插入突变c.2033dupC(p.Pro678Thrfs*22),进一步检测表明该突变在家系内与疾病表型共分离。结论 N F 1基因c.2033dupC突变是该家系的致病突变,针对致病基因编码外显子较多的遗传性疾病的检测,高通量测序技术具有显著优势。

Objective To detect gene mutation in a neurofibromatosis type 1 （NF1） family, and provide genetic counseling and guidance for prenatal diagnosis. Methods We performed targeted next-generation sequencing （NGS） to identify mutations in NFI gene coding region and its adjacent sequence in a patient with typical symptoms from the family. Sanger sequencing was used to validate suspicious mutation sites found by NGS. We also detected whether the mutation separated with phenotypes in this family. Results In this NF1 pedigree, we found a small insertion in exon 18 of NF1 gene, c.2033dupC（p.Pro678Thrfs＊22）, and this mutation separated with phenotypes in this family. Conclusion c.2033dupC mutation in NF1 gene is the pathogenic mutation for this NF1 family, high-throughput NGS has significant advantage in mutation detection of inherited diseases, especially in disease whose causing genes are with a great many exons.