Sharafi Parisa, Ayter Sükriye
a Faculty of Medicine , TOBB University of Economics and Technology , Ankara , Turkey.
J Neurogenet. 2018 Mar-Jun;32(2):65-77. doi: 10.1080/01677063.2018.1456538. Epub 2018 Apr 12.
Neurofibromatosis type 1 (NF1) is the most common neurogenetic disorder worldwide, caused by mutations in the (NF1) gene. Although NF1 is a single-gene disorder with autosomal-dominant inheritance, its clinical expression is highly variable and unpredictable. NF1 patients have the highest known mutation rate among all human disorders, with no clear genotype-phenotype correlations. Therefore, variations in NF1 mutations may not correlate with the variations in clinical phenotype. Indeed, for the same mutation, some NF1 patients may develop severe clinical symptoms whereas others will develop a mild phenotype. Variations in the mutant NF1 allele itself cannot account for all of the disease variability, indicating a contribution of modifier genes, environmental factors, or their combination. Considering the gene structure and the interaction of neurofibromin protein with cellular components, there are many possible candidate modifier genes. This review aims to provide an overview of the potential modifier genes contributing to NF1 clinical variability.
1型神经纤维瘤病（NF1）是全球最常见的神经遗传性疾病，由（NF1）基因突变引起。尽管NF1是一种具有常染色体显性遗传的单基因疾病，但其临床表型高度可变且不可预测。在所有人类疾病中，NF1患者的已知突变率最高，且不存在明确的基因型-表型相关性。因此，NF1突变的差异可能与临床表型的差异无关。事实上，对于相同的突变，一些NF1患者可能会出现严重的临床症状，而另一些患者则会表现出轻微的表型。突变的NF1等位基因本身的差异并不能解释所有的疾病变异性，这表明修饰基因、环境因素或它们的组合起到了一定作用。考虑到基因结构以及神经纤维瘤蛋白与细胞成分的相互作用，存在许多可能的候选修饰基因。本综述旨在概述可能导致NF1临床变异性的潜在修饰基因。
