Abstract

INTRODUCTION

Neurofibromatosis type I and type 2 (NF1 and NF2) are two rare autosomal dominant neurocutaneous genetic disorders that are diagnosed based on clinical diagnostic criteria of the National Institutes of Health Consensus. Due to increased malignancy risks and age-related penetrance, NGS-based diagnosis methods should be used for early diagnosis. However, molecular diagnosis of the NF1 and NF2 genes are challenging owing to the large size of genes, and the lack of mutation hotspots. In this study, we present 67 patients between 2016-2019 who were investigated for NF1 and NF2 genes with the next generation sequencing (NGS). We aimed to show the effectiveness of NGS-based molecular genetic diagnoses and contribute to establishing the variant spectrum in the Turkish population.

METHODS

Patients who met the diagnostic criteria were included in this study. After DNA extraction from peripheric blood samples, an NGS-based panel that includes both NF1 and NF2 genes was performed. Results were evaluated using ACMG 2015 criteria and in silico bioinformatics tools.

RESULTS

39 of 67 total patients revealed various variants (39/67, ~%58). The variant distribution was as follows; 15 frameshift, 8 nonsense, 7 missense, 6 splice sites, and three insertion/deletion. Novel variants ratio was 23/39 (22 NF1, 1 NF2, ~%59). The classification according to clinical significance was as follows: 23 pathogenic, 14 likely pathogenic, and one VUS according to ACMG 2015 criteria.

DISCUSSION AND CONCLUSION

Our results suggested that a genetic screening using an NGS panel is more useful and helpful to provide early diagnosis and genetic counseling and have a positive impact on patient follow-up.