Guo Xiao-Hui, Jin Xin, Wang Bin, Wang Zhao-Yan
Senior Department of Ophthalmology, the Third Medical Center of PLA General Hospital, Beijing 100039, China.
Department of Otolaryngology, Peking Union Medical College Hospital, Beijing 100730, China.
Int J Ophthalmol. 2023 Jan 18;16(1):47-52. doi: 10.18240/ijo.2023.01.07. eCollection 2023.
To detect the pathogenic gene variant in a family with neurofibromatosis type 1 (NF1).
This patient with NF1 was sequenced using target sequence capture and high-throughput sequencing technology. After detecting the suspicious pathogenic variant type, the pathogenic variant sites of the patient and the patient's family members were verified by multiple ligation dependent probe amplification and Sanger sequencing. Sift, polyphen-2, Mutation Taster and GERP++ software were used to predict the pathogenicity of the unknown loci. The clinical data, diagnosis and treatment process of the patients were reviewed. Using the keyword "NF1; frameshift pathogenic variant", relevant literature was gathered for analysis from Chinese and international databases, with articles dating from the establishment of each database to April 2022.
A heterozygous frameshift pathogenic variant of in exon 33 was detected in the patient. The insertion of adenine in coding region 4486 resulted in the replacement of isoleucine with asparagine in protein 1497. Sanger sequencing validation and segregation analysis were performed, which demonstrated that the gene was cosegregated with the disease phenotype in this family. This study identified a novel heterozygous frameshift mutation c.4486dupA (p.I1497Nfs*12). Relevant literature retrieval found 7 Chinese articles and 12 foreign articles. With gene mutation, mutation types are diverse, including point mutation, frameshift mutation, splice site mutation, exon mutation, chimeric mutation and de novo mutation. Foreign reports are based on autosomal dominant inheritance.
This study's results demonstrate that a novel deletion in exon 33 caused NF1 in this Chinese family, expanding the mutational spectrum of the gene.
检测1型神经纤维瘤病（NF1）家系中的致病基因变异。
采用靶向序列捕获和高通量测序技术对该NF1患者进行测序。在检测到可疑的致病变异型后，通过多重连接依赖探针扩增和桑格测序对患者及其家庭成员的致病变异位点进行验证。使用Sift、polyphen-2、Mutation Taster和GERP++软件预测未知位点的致病性。回顾患者的临床资料、诊断和治疗过程。以“NF1；移码致病变异”为关键词，从中国和国际数据库收集自各数据库建立至2022年4月的相关文献进行分析。
在患者中检测到第33外显子杂合移码致病变异。编码区4486处腺嘌呤的插入导致蛋白质1497位异亮氨酸被天冬酰胺取代。进行了桑格测序验证和分离分析，结果表明该基因在该家系中与疾病表型共分离。本研究鉴定出一种新的杂合移码突变c.4486dupA（p.I1497Nfs*12）。相关文献检索发现中文文章7篇，外文文章12篇。NF1基因突变类型多样，包括点突变、移码突变、剪接位点突变、外显子突变、嵌合突变和新发突变。国外报道基于常染色体显性遗传。
本研究结果表明，第33外显子的一种新缺失导致了这个中国家系中的NF1，扩展了NF1基因的突变谱。
