Viskochil David
Department of Pediatrics, University of Utah, Salt Lake City 84132, USA.
J Child Neurol. 2002 Aug;17(8):562-70; discussion 571-2, 646-51. doi: 10.1177/088307380201700804.
Neurofibromatosis 1 serves as a paradigm for understanding the principles of human genetics. The concepts of gene mutation, penetrance of the condition, variable clinical expressivity, mosaicism, age-dependent expression of clinical manifestations, and pleiotropy are evident in this autosomal dominant condition. The lack of genotype-phenotype correlation, except the whole-gene deletion phenotype, leads to speculation on modifiers of the haploinsufficient state of the NF1 gene product neurofibromin. The variant form of neurofibromatosis, neurofibromatosis Noonan's syndrome, suggests potential interaction of independent biochemical pathways. Identification of the NF1 gene led to the discovery of its role in ras signal transduction. Neurofibromin is a negative regulator of intracellular ras signaling. This observation now provides the framework for the development of rational medical therapies. In addition, knowledge of the molecular basis of the variable expression of clinical manifestations could provide better anticipatory guidance and more effective management of the medical complications that are associated with this condition.
神经纤维瘤病1型是理解人类遗传学原理的一个范例。基因突变、疾病的外显率、可变的临床表型、镶嵌现象、临床表现的年龄依赖性表达以及多效性等概念在这种常染色体显性疾病中都很明显。除了全基因缺失表型外，缺乏基因型与表型的相关性引发了对NF1基因产物神经纤维瘤蛋白单倍体不足状态的修饰因子的推测。神经纤维瘤病的变异形式，即努南综合征型神经纤维瘤病，提示了独立生化途径之间的潜在相互作用。NF1基因的鉴定导致了其在ras信号转导中作用的发现。神经纤维瘤蛋白是细胞内ras信号传导的负调节因子。这一观察结果现在为合理的医学治疗发展提供了框架。此外，了解临床表现可变表达的分子基础可以为这种疾病相关的医学并发症提供更好的预期指导和更有效的管理。
