Identifying a novel frameshift pathogenic variant in a Chinese family with neurofibromatosis type 1 and review of literature
Author:
Corresponding Author:

Bin Wang. Department of Otolaryngology, Peking Union Medical College Hospital, No.1 Shuaifuyuan, Dongcheng District, Beijing 100730, China. wangbin780@126.com; Zhao-Yan Wang. Senior Department of Ophthalmology, the Third Medical Center of PLA General Hospital, No.69 Yongding Road, Haidian District, Beijing 100039, China. wzyli2468@126.com

Affiliation:

Clc Number:

Fund Project:

Supported by National High Level Hospital Clinical Research Funding (No.2022-PUMCH-A-031).

  • Article
  • |
  • Figures
  • |
  • Metrics
  • |
  • Reference
  • |
  • Related
  • |
  • Cited by
  • |
  • Materials
  • |
  • Comments
    Abstract:

    AIM: To detect the pathogenic gene variant in a family with neurofibromatosis type 1 (NF1). METHODS: 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. RESULTS: A heterozygous frameshift pathogenic variant of NF1 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 NF1 gene was cosegregated with the disease phenotype in this family. This study identified a novel NF1 heterozygous frameshift mutation c.4486dupA (p.I1497Nfs*12). Relevant literature retrieval found 7 Chinese articles and 12 foreign articles. With NF1 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. CONCLUSION: This study’s results demonstrate that a novel deletion in exon 33 caused NF1 in this Chinese family, expanding the mutational spectrum of the NF1 gene.

    Reference
    Related
    Cited by
Get Citation

Xiao-Hui Guo, Xin Jin, Bin Wang, et al. Identifying a novel frameshift pathogenic variant in a Chinese family with neurofibromatosis type 1 and review of literature. Int J Ophthalmol, 2023,16(1):47-52

Copy
Share
Article Metrics
  • Abstract:
  • PDF:
  • HTML:
  • Cited by:
Publication History
  • Received:April 25,2022
  • Revised:November 03,2022
  • Adopted:
  • Online: December 23,2022
  • Published: