11例散发型Ⅰ型神经纤维瘤病患者NF1基因突变分析  

Analysis of NF1 gene mutations among eleven sporadic patients with neurofibromatosis type 1

作　　者：彭春艳 马誓 唐向兰[1,2] 杨季云 Peng Chunyan, Ma Shi, Tang Xianglan, Yang Jiyun(Laboratory for Disease Gene Study, School of Medicine, Sichuan Provincial People＇s Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China; Prenatal Diagnosis Center, Sichuan Provincial People＇s Hospital, Chengdu, Sichuan 610072, Chin)

机构地区：[1]电子科技大学医学院、电子科技大学附属医院·四川省人民医院人类疾病基因研究重点实验室,成都610054 [2]四川省人民医院产前诊断中心,成都610072

出　　处：《中华医学遗传学杂志》2018年第4期480-483,共4页Chinese Journal of Medical Genetics

基　　金：四川省科研院所科技成果转化资金项目（2016YSZH0032）;成都市科技局科技惠民计划项目（2015-HM02-00094-SF）

摘　　要：目的探讨散发型I型神经纤维瘤病的遗传病因，为家系的遗传咨询和产前诊断提供理论依据。方法应用芯片靶向性捕获高通量测序检测11例散发型I型神经纤维瘤病患者的NFl、NF2基因突变。通过多个突变数据库及实验室外显子组测序的数据库过滤，Sanger测序进行家系分析。结果在11例散发型I型神经纤维瘤病患者检出11个突变，包括2个剪接位点突变、1个错义突变、2个无义突变、6个移码突变。在公共数据库及1775名正常对照外显子测序数据中，均未检索到这11个突变位点。经家系验证，先证者父母均不携带该突变。其中，7个突变位点与I型神经纤维瘤病相关已有报道，4个突变位点为未报道过的致病突变。两个家系的产前基因检测结果显示胎儿均未携带与先证者相同的突变。结论明确了11例散发型神经纤维瘤病的遗传病因，为家系的遗传咨询和产前诊断提供了理论依据；新突变的检出丰富了NF1基因突变谱。Objective To explore the genetic etiology for 11 sporadic patients with neurofibromatosis type 1. Methods Chip targeting capture and high-throughput sequencing were employed to detect potential mutations of NF1 and NF2 genes among the 11 patients. The data was filtered through multiple mutational databases and in-house whole exome sequence database. Sanger sequencing was used for analysis of family members of the patients. Results Eleven pathogenic variants were found among the 11 patients, which included two splicing mutations, one missense mutation, two nonsense mutations, and six frame-shifting mutations. None of the mutations was recorded by the public database or the in-house database generated from 1775 samples through whole exome sequencing. None of the unaffected parents carried the same mutation. Seven mutations were associated with neurofibromatosis type 1 previously, while the remaining four were discovered for the first time. Prenatal diagnosis of two high-risk pregnancies suggested that neither fetus has inherited the NF1 mutation from their affected parents. Conclusion Identification of causative mutations in patients with sporadic-type neurofibromatosis type 1 has provided a basis for genetic counseling. The four novel mutations have enriched the spectrum of NF1 gene mutations.

关 键 词：神经纤维瘤病 高通量测序 NF1基因 产前诊断 

分 类 号：R440[医药卫生—诊断学] R596.1[医药卫生—临床医学]