Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110; email:
Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110.
Annu Rev Pathol. 2017 Jan 24;12:53-74. doi: 10.1146/annurev-pathol-052016-100228.
Neurofibromatosis type 1 (NF1) is a common neurogenetic disorder in which affected children and adults are predisposed to the development of benign and malignant nervous system tumors. Caused by a germline mutation in the NF1 tumor suppressor gene, individuals with NF1 are prone to optic gliomas, malignant gliomas, neurofibromas, and malignant peripheral nerve sheath tumors, as well as behavioral, cognitive, motor, bone, cardiac, and pigmentary abnormalities. Although NF1 is a classic monogenic syndrome, the clinical features of the disorder and their impact on patient morbidity are variable, even within individuals who bear the same germline NF1 gene mutation. As such, NF1 affords unique opportunities to define the factors that contribute to disease heterogeneity and to develop therapies personalized to a given individual (precision medicine). This review highlights the clinical features of NF1 and the use of genetically engineered mouse models to define the molecular and cellular pathogenesis of NF1-associated nervous system tumors.
神经纤维瘤病 1 型（NF1）是一种常见的神经遗传性疾病，受影响的儿童和成人易患良性和恶性神经系统肿瘤。NF1 由 NF1 肿瘤抑制基因的种系突变引起，NF1 个体易患视神经胶质瘤、恶性胶质瘤、神经纤维瘤和恶性外周神经鞘瘤，以及行为、认知、运动、骨骼、心脏和色素异常。尽管 NF1 是一种经典的单基因综合征，但该疾病的临床特征及其对患者发病率的影响存在差异，即使在携带相同种系 NF1 基因突变的个体中也是如此。因此，NF1 为定义导致疾病异质性的因素以及为特定个体开发个性化治疗方法（精准医学）提供了独特的机会。这篇综述强调了 NF1 的临床特征以及利用基因工程小鼠模型来定义 NF1 相关神经系统肿瘤的分子和细胞发病机制。
