Mao Bin, Chen Siyu, Chen Xin, Yu Xiumei, Zhai Xiaojia, Yang Tao, Li Lulu, Wang Zheng, Zhao Xiuli, Zhang Xue
Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
Department of Obstetrics and Gynecology, the First Affiliated Hospital of Hebei North University, Zhangjiakou, 075061, China.
BMC Med Genet. 2018 Jun 18;19(1):101. doi: 10.1186/s12881-018-0615-8.
Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder caused by a heterozygous germline mutation in the tumor suppressor gene NF1. Because of the existence of highly homologous pseudogenes, the large size of the gene, and the heterogeneity of mutation types and positions, the detection of variations in NF1 is more difficult than that for an ordinary gene.
In this study, we collected samples from 23 patients among 46 study participants from 12 unrelated Chinese families with NF1. We used a combination of Sanger sequencing, targeted next-generation sequencing, and multiplex ligation-dependent probe amplification to identify potential mutations of different types.
Seven recurrent mutations and four novel mutations were identified with the aforementioned methods, which were subsequently confirmed by either restriction fragment length polymorphism analysis or Sanger sequencing. Truncating mutations accounted for 73% (8/11) of all mutations identified. We also exhaustively investigated the clinical manifestations of NF1 in patients via acquired pathography, photographs and follow-up. However, no clear genotype-phenotype correlation has been found to date.
In conclusion, the novel mutations identified broaden the spectrum of NF1 mutations in Chinese; however, obvious correlations between genotype and phenotype were not observed in this study.
1型神经纤维瘤病（NF1）是一种常见的常染色体显性疾病，由肿瘤抑制基因NF1的杂合种系突变引起。由于存在高度同源的假基因、基因规模大以及突变类型和位置的异质性，NF1变异的检测比普通基因更困难。
在本研究中，我们从12个无血缘关系的中国NF1家庭的46名研究参与者中的23名患者收集样本。我们使用桑格测序、靶向二代测序和多重连接依赖探针扩增相结合的方法来鉴定不同类型的潜在突变。
通过上述方法鉴定出7个复发性突变和4个新突变，随后通过限制性片段长度多态性分析或桑格测序予以证实。截短突变占所有鉴定出的突变的73%（8/11）。我们还通过后天影像学、照片和随访详尽地研究了患者的NF1临床表现。然而，迄今为止尚未发现明确的基因型-表型相关性。
总之，鉴定出的新突变拓宽了中国NF1突变谱；然而，本研究未观察到基因型与表型之间存在明显相关性。
