13例Ⅰ型神经纤维瘤病患儿的基因变异分析

Analysis of NF1 gene variants among thirteen patients with neurofibromatosis type 1

目的探讨Ⅰ型神经纤维瘤病患儿的NF1基因变异情况,为家系的遗传咨询和临床诊治提供依据。方法应用高通量测序技术检测13例Ⅰ型神经纤维瘤病患儿的NF1、NF2基因变异情况,100名正常人作为对照。利用Sanger测序技术对可疑位点和家系成员进行验证。结果13例患儿共检测到13个NF1基因变异位点,包括NF1杂合缺失1例、错义变异3例、无义变异3例和移码变异6例,其中,10个均已报道与I型神经纤维瘤病相关,c.4180A>T(p.Asn1394Tyr)、c.4217dupT(p.Leu1406fs)和c.1753dupT(p.Leu585Phefs*3)为未报道过的新变异,根据美国医学遗传学与基因组学学会指南,c.4180A>T(p.Asn1394Tyr)判定为可能致病性变异(PS2+PM1+PM2+PP2),c.4217dupT(p.Leu1406fs)和c.1753dupT(p.Leu585Phefs*3)均判定为致病性变异(PVS1+PS2+PM2)。结论NF1基因变异可能为这些患儿的致病原因,新变异位点的检出丰富了NF1基因的变异谱。

Objective To detect variants of NF1 gene among thirteen patients with neurofibromatosis type 1.Methods Genomic DNA was extracted from peripheral blood samples of the patients.High-throughput sequencing was employed to detect potential variants of the NF1 and NF2 genes.Results Thirteen pathogenic variants were identified among the patients,which included one NF1 deletion,three missense variants,three nonsense variants and six frameshifting variants.Among these,10 variants have been associated with neurofibromatosis type 1.c.4180A>T(p.Asn1394Tyr),c.4217dupT(p.Leu1406fs)and c.1753dupT(p.Leu585Phefs*3)were unreported previously.Based on the guidelines of the American College of Medical Genetics and Genomics,c.4180A>T(p.Asn1394Tyr)was predicted to be likely pathogenic(PS2+PM1+PM2+PP2),while c.4217dupT(p.Leu1406fs)and c.1753dupT(p.Leu585Phefs*3)were predicted to be pathogenic(PVS1+PS2+PM2).Conclusion Variants of the NF1 gene probably underlay the disease among these children.Above findings have enriched the the spectrum of NF1 gene variants.