Upadhyaya M, Shaw D J, Harper P S
Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, U.K.
Hum Mutat. 1994;4(2):83-101. doi: 10.1002/humu.1380040202.
Neurobromatosis type 1 (NF1) is one of the commonest genetic disorders in humans. The gene for NF1 was cloned in 1990. The protein encoded by the gene (neurofibromin) has extensive sequence homology with GTPase-activating protein (GAP). Despite screening the whole coding region of the gene for large and medium size rearrangements and approximately 40% of the coding region of the gene for small alterations, only 45 germ-line mutations have been reported in more than 500 unrelated patients. Of these, 25 mutations involve small changes in the gene, of which 17 (68%) result in the formation of an inappropriate stop codon. A "hot spot" for mutations has not been identified. The high mutation rate at this locus and the general difficulty in identifying mutations are discussed. A complete understanding of the structure and function of the NF1 gene awaits further detailed studies of both naturally occurring and in vitro-generated mutations.
1型神经纤维瘤病（NF1）是人类最常见的遗传性疾病之一。NF1基因于1990年被克隆。该基因编码的蛋白质（神经纤维瘤蛋白）与GTP酶激活蛋白（GAP）具有广泛的序列同源性。尽管对该基因的整个编码区进行了大、中规模重排筛查，并对该基因约40%的编码区进行了小改变筛查，但在500多名无亲缘关系的患者中仅报告了45种生殖系突变。其中，25种突变涉及基因的小变化，其中17种（68%）导致形成不适当的终止密码子。尚未发现突变的“热点”。讨论了该位点的高突变率以及鉴定突变的一般困难。对NF1基因结构和功能的全面理解有待对自然发生的和体外产生的突变进行进一步详细研究。
