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 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.

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 gene.