Impacts of NF1 Gene Mutations and Genetic Modifiers in Neurofibromatosis Type 1

Abstract

Neurofibromatosis type 1 (NF1) is a tumor predisposition genetic disorder that directly affects more than 1 in 3,000 individuals worldwide. It results from mutations of the NF1 gene and shows almost complete penetrance. NF1 patients show high phenotypic variabilities, including cafe-au-lait macules, freckling, or other neoplastic or non-neoplastic features. Understanding the underlying mechanisms of the diversities of clinical symptoms might contribute to the development of personalized healthcare for NF1 patients. Currently, studies have shown that the different types of mutations in the NF1 gene might correlate with this phenomenon. In addition, genetic modifiers are responsible for the different clinical features. In this review, we summarize different genetic mutations of the NF1 gene and related genetic modifiers. More importantly, we focus on the genotype–phenotype correlation. This review suggests a novel aspect to explain the underlying mechanisms of phenotypic heterogeneity of NF1 and provides suggestions for possible novel therapeutic targets to prevent or delay the onset and development of different manifestations of NF1.

Canonical and uncanonical pathogenic germline variants in colorectal cancer patients by next-generation sequencing in a European referral center

“…NF1 ). 19 , 20 We first retrieved NGS sequencing data for CPGs that are firmly associated with CRC. Thereafter, irrespective of the clinical picture, the entire panel was interrogated, and both PVs and variants of uncertain significance (VUS) were annotated.…”

Genotype-Phenotype Correlations in Neurofibromatosis Type 1: Identification of Novel and Recurrent NF1 Gene Variants and Correlations with Neurocognitive Phenotype

“…On the other hand, the influence of variants in other genes on NF1 phenotype cannot be excluded. Several studies showed that different mutations of NF1 and related genetic modifiers might contribute together to clinical features in NF1, including tumor development, making the scenario more complex [ 119 ]. It will be very important to perform this analysis in our cohort of patients in the future.…”

Prevalence of Germline Mutations in Cancer Predisposition Genes in Patients with Pancreatic Cancer or Suspected Related Hereditary Syndromes: Historical Prospective Analysis

“…In the employed panel, high-penetrance genes involve a lifetime risk of cancer >= 40%, while the risk associated with “moderate” genes is usually <40%, although this notion does not invariably apply to fully penetrant methylated CpG islands (CpGs) (e.g., NF1 ) [ 25 ]. We first retrieved NGS sequencing data for CpGs that were strongly associated with PDAC, and both PVs and VUS were annotated.…”