Abstract
BackgroundNeurofibromatosis type 1 (NF1) is a dominantly inherited tumor predisposition syndrome that targets the peripheral nervous system. It is caused by mutations of the NF1 gene which serve as a negative regulator of the cellular Ras/MAPK (mitogen-activated protein kinases) signaling pathway. Owing to the complexity in some parts of clinical diagnoses and the need for better understanding of its molecular relationships, a genetic characterization of this disorder will be helpful in the clinical setting.MethodsIn this study, we present a customized targeted gene panel of NF1/KRAS/BRAF/p53 and SPRED1 genes combined with Multiple Ligation-Dependent Probe Amplification analysis for the NF1 mutation screening in a cohort of patients clinically suspected as NF1.ResultsIn this study, we identified 73 NF1 mutations and two BRAF novel variants from 100 NF1 patients who were suspected as having NF1. These genetic alterations are heterogeneous and distribute in a complicated way without clustering in either cysteine–serine-rich domain or within the GAP-related domain. We also detected fifteen multi-exon deletions within the NF1 gene by MLPA Analysis.ConclusionsOur results suggested that a genetic screening using a NGS panel with high coverage of Ras–signaling components combined with Multiple Ligation-Dependent Probe Amplification analysis will enable differential diagnosis of patients with overlapping clinical features.
Highlights
Neurofibromatosis type 1 (NF1) is a dominantly inherited tumor predisposition syndrome that targets the peripheral nervous system
Genetic alterations identified from a targeted next-generation sequencing (NGS) gene panel screening A total of 100 individuals from 95 families who were clinically suspected as carrying NF1 were referred for this genetic testing
We have identified seventy-three NF1 mutations (Table 2) and two BRAF novel variants from a targeted NGS gene panel of NF1/KRAS/BRAF/p53 and SPRED1 analyses
Summary
Neurofibromatosis type 1 (NF1) is a dominantly inherited tumor predisposition syndrome that targets the peripheral nervous system It is caused by mutations of the NF1 gene which serve as a negative regulator of the cellular Ras/MAPK (mitogen-activated protein kinases) signaling pathway. Neurofibromatosis type 1 (MIM# 162200) is a very common genetic disorder affecting approximately 1 in 3000–4000 individuals worldwide with the penetrance of the mutant gene being close to 100% by 5 years of age [1,2,3,4] It is presented with the occurrence of Café-au-lait macules, Lisch nodules, axillary freckling and NF1 is caused by mutations of the NF1 gene which maps to chromosome 17q11.2. Other mutations are single- or multi-exon deletions or duplications and microdeletions encompassing NF1 and its neighboring genes [12,13,14,15,16,17,18,19,20,21,22]
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