Genotype–Phenotype Correlation of Novel NF1 Gene Variants Detected by NGS in Patients with Neurofibromatosis Type 1

Abstract

Neurofibromatosis type 1 (NF1) is an inherited tumor predisposition syndrome. The high susceptibility to benign-malignant tumors and frequency of complications have revealed the importance of genetic molecular diagnosis and regular follow-up of patients. The aim of this study was to identify the genetic mutations that cause the disease and provide genotype/phenotype correlations. The patients with NF1 assessed in the genetic outpatient clinic between 2018 and 2020 were included in the study. The NF1 gene was analyzed by next generation sequencing (NGS) method. Patient's demografic features and the results of NF1 gene analysis were investigated retrospectively. Café au lait spots were present in all 40 patients included in the study. Lisch nodule was observed in 20%, optic glioma in 10%, neurofibroma in 12.5%, hamartoma in 10%, short stature in 10% of patients. Cranial MRI abnormalities were detected in 55% of patients. We detected four novel mutations which were not reported before in the literature; p.S2460*, p.Q1360sFS*20, p.K1457* and p.K918*.Prediction of complications that may arise in patients according to mutations and information about genotype-phenotype correlations can be helpful in the management of the disease. Early diagnosis, informing families about NF1 disease, providing genetic counseling, and regular follow-up of patients by a team of experts from different branches are important in terms of minimizing the mortality and morbidity of NF1.