散发型Ⅰ型神经纤维瘤的基因突变鉴定与家系分析

Gene diagnosis and pedigree analysis in families of sporadic type Ⅰ neurofi broma family

目的对一例先证者为Ⅰ型神经纤维瘤病的患儿进行基因突变鉴定与家系研究。方法采用高通量测序技术对NF1基因进行点突变和基因拷贝数检测,应用MLPA技术对患者NF1、NF2基因进行大片段变异研究,采用STR连锁分析对先证者及其父母进行亲缘关系鉴定,对其父母进行体格检查和表型分析,采用Sanger测序方法对高通量测序点突变进行先证者和家系验证。结果高通量测序检出患者NF1基因致病变异c.1013A>G,该突变为已报道的Ⅰ型神经纤维瘤致病突变,其生物学父母未见神经纤维瘤表型且无上述突变。结论该神经纤维瘤患儿是由NF1新发突变所致,高通量测序技术对检测致病基因含较多外显子的遗传性疾病具有显著优势。

Objective:To identify the genetic ecology and family analyse a patient with neurofibromatosis type 1.Methods:High-throughput sequencing was used to detect the point mutation and copy number of NF1 and NF2 gene.MLPA was used to verify the large-segment mutation of NF1 and NF2 gene.STR linkage analysis was used to identify the relationship between the proband parents and their parents.Physical examination and phenotypic analysis,Sanger sequencing was used to analyze the point mutation of NF1 and NF2 gene in the parents.Results:High-throughput sequencing showed that the pathogenic mutation of NF1 gene was c.1013A>G.The mutation was a reported neurofibroma in type I pathogenic mutation.The biological parents had no neurofibroma phenotype and no NF1 gene mutation.Conclusion:The neurofibroma is caused by a new mutation in NF1,and high-throughput sequencing has a significant advantage in detecting genetic diseases with more exons in the pathogenic gene.