NF1 Mutations Analysis Using Whole Exome Sequencing Technique in 11 Unrelated Iranian Families with Neurofibromatosis Type 1

Background Neurofibromatosis is an autosomal dominant disease. It affects one in 2,700 to 3,300 people. The main gene mutated in the disease is a tumor suppressor protein called neurofibromin. There are several categories, the most important of which is divided into two types of type I and type 2 neurofibromatosis. Here, we aimed to identify the underlying genetic defect in eleven Iranian families with Neurofibromatosis type 1. Materials and Methods In this cross-sectional descriptive study, 18 patients were studied in 11 Iranian families. After clinical examination by the relevant specialist, DNA extraction was performed on the affected individuals, and then whole exome sequencing was used for accurate diagnosis. Results 11 individuals (4 males and 7 females) with average age 26± 1.18 year participated in the study. Precise diagnosis of type 1 neurofibromatosis was made. The location of the gene and even the type of mutation was also determined. These mutations, reported in eleven families include 4 deletions (c.747_75 del ATTTG, c.1458.1459delAA, c.1186-13delT, c.2804_2804delA), 3 nonsense mutations (Arg1306x, R1276X, L276X,), 2 splice site mutation (c.1261-2A>G, c.1185+1G>T), a silent mutation (c.3395G>A), and an Insertion mutation (c.4446_4447insT). Conclusion In conclusion, owing to the complexity of the diagnosis and, in some cases and the need to better- understand the molecular mechanisms of the disease, determining the genetic mutation profile of the disease may be of great help in better understanding the disease and Whole Exome sequencing is an extremely efficient method to identify possible disease-causing mutations.