1型神经纤维瘤病(NF1)是一种肿瘤易感性遗传性疾病,直接影响全球3,000人中的1人。它是由NF1基因的突变引起的,并显示出几乎完全的外显率。NF1患者表现出高表型变异,包括咖啡馆-au-lait黄斑,雀斑,或其他肿瘤或非肿瘤特征。了解临床症状多样性的潜在机制可能有助于NF1患者个性化医疗保健的发展。目前,研究表明,NF1基因中不同类型的突变可能与这种现象有关。此外,遗传修饰剂负责不同的临床特征。在这次审查中,我们总结了NF1基因的不同基因突变和相关的遗传修饰。更重要的是,我们关注基因型-表型相关性。这篇综述提出了一个新的方面来解释NF1表型异质性的潜在机制,并为可能的新治疗靶标提供了建议,以预防或延迟NF1不同表现的发生和发展。
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.