Shen M H, Harper P S, Upadhyaya M
Institute of Medical Genetics, College of Medicine, University of Wales, Heath Park, Cardiff, UK.
Hum Mol Genet. 1993 Nov;2(11):1861-4. doi: 10.1093/hmg/2.11.1861.
Despite the extensive search for disease causing mutations in exons 28-36 of the neurofibromatosis type 1 (NF1) gene, the NF1 specific mutations so far documented account for only a small proportion of all NF1 cases. In this study, we have used 8 sets of new primers to amplify sequences throughout the NF1 gene, including 10 different exons and their flanking intron sequences. The derived PCR products from 150 independent NF1 patients and 50 normal controls were examined by heteroduplex analysis on Hydrolink gels. Three novel mutations were identified and characterised. Two of these mutations include the same 3-bp deletion (AAT) within exon 17 with a silent codon change from ACA (threonine) to ACG (threonine) and a loss of the codon ATG (methionine). The third mutation is a 10-bp deletion (TTCTCTTGGA) within exon 44 resulting in the formation of an inappropriate stop codon. These results should be useful for the further elucidation of the molecular basis of NF1.
尽管对1型神经纤维瘤病（NF1）基因第28至36外显子中致病突变进行了广泛搜索，但迄今为止记录的NF1特异性突变仅占所有NF1病例的一小部分。在本研究中，我们使用了8组新引物来扩增整个NF1基因的序列，包括10个不同的外显子及其侧翼内含子序列。通过在Hydrolink凝胶上进行异源双链分析，对来自150例独立NF1患者和50例正常对照的PCR产物进行了检测。鉴定并表征了三个新突变。其中两个突变包括第17外显子内相同的3个碱基缺失（AAT），密码子由ACA（苏氨酸）变为ACG（苏氨酸）且密码子ATG（甲硫氨酸）缺失，为沉默突变。第三个突变是第44外显子内10个碱基的缺失（TTCTCTTGGA），导致形成一个不适当的终止密码子。这些结果将有助于进一步阐明NF1的分子基础。
