Ⅰ型神经纤维瘤病一个家系及散发病例1例的NF1基因变异分析

Analysis of NF1 gene variants in a Chinese pedigree and a sporadic patient with Neurofibromatosis type 1

目的对Ⅰ型神经纤维瘤病(NF1)1个家系和1例散发病例的NF1基因进行变异分析,探讨遗传学病因。方法回顾性分析2022年10月22日于厦门大学附属第一医院就诊的1个NF1家系及另1例散发NF1患儿的临床资料,提取患者外周血基因组DNA进行临床全外显子组捕获和测序,确定候选基因变异位点,针对变异位点进行Sanger测序验证。结果NF1家系中,先证者及其母亲与妹妹均携带NF1基因第25外显子c.3251delC变异,先证者父亲未携带该变异;散发NF1病例携带NF1基因第32外显子c.4312_4314delGAA变异,其父母均未携带该变异。根据美国医学遗传学与基因组学学会(ACMG)相关指南,c.3251delC与c.4312_4314delGAA均被评定为致病性变异(PVS1+PS4_Supporting+PM2_Supporting+PP4;PS2+PS4_Moderate+PM2_Supporting+PM4+PP4)结论NF1基因c.3251delC与c.4312_4314delGAA变异可能分别为该家系及散发病例罹患NF1的致病原因。

Objective To explore the genetic basis for a Chinese pedigree and a sporadic case with Neurofibromatosis type 1(NF1).Methods Clinical data of the pedigree and the sporadic case were collected.Genomic DNA was extracted from peripheral venous blood samples and subjected to whole exome sequencing.Candidate variants were validated by Sanger sequencing and bioinformatic analysis.Results All patients from the pedigree were found to harbor a c.3251delC variant in exon 25 of the NF1 gene,whilst a c.4312_4314delGAA variant was found in exon 32 of the NF1 gene in the sporadic case.Conclusion Variants of the NF1 gene may account for the occurrence of NF1 in this pedigree and sporadic case.