Wang Wei, Wei Cheng-Jiang, Cui Xi-Wei, Li Yue-Hua, Gu Yi-Hui, Gu Bin, Li Qing-Feng, Wang Zhi-Chao
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Neurol. 2021 Sep 8;12:704639. doi: 10.3389/fneur.2021.704639. eCollection 2021.
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.
1型神经纤维瘤病（NF1）是一种肿瘤易感性遗传疾病，全球每3000多人中就有1人直接受其影响。它由NF1基因突变引起，几乎具有完全的外显率。NF1患者表现出高度的表型变异性，包括咖啡斑、雀斑或其他肿瘤性或非肿瘤性特征。了解临床症状多样性的潜在机制可能有助于为NF1患者开发个性化医疗。目前，研究表明NF1基因的不同类型突变可能与这一现象相关。此外，遗传修饰因子也导致了不同的临床特征。在本综述中，我们总结了NF1基因的不同基因突变和相关遗传修饰因子。更重要的是，我们关注基因型与表型的相关性。本综述提出了一个新的角度来解释NF1表型异质性的潜在机制，并为预防或延缓NF1不同表现的发生和发展提供可能的新治疗靶点的建议。
