一个Ⅰ型神经纤维瘤病家系的基因突变分析  

NF1 Mutation Analysis in a Family with Neurofibromatosis Type Ⅰ

作　　者：李丹丹[1] 王进[1] 梁婷[1] 马兰茗[1] 刘明[1] 

机构地区：[1]哈尔滨医科大学附属第四医院眼科,黑龙江哈尔滨150001

出　　处：《现代生物医学进展》2013年第32期6261-6263,共3页Progress in Modern Biomedicine

基　　金：哈尔滨市科技创新人才研究专项资金项目(青年科技创新人才2010RFQXS075)

摘　　要：目的:Ⅰ型神经纤维瘤病是一种常见的常染色体显性遗传病,主要累及皮肤和神经系统。其临床表现多样,主要以"咖啡牛奶斑"、皮肤神经纤维瘤、虹膜Lisch结节、腋窝和腹股沟斑点为特征,Ⅰ型神经纤维瘤病由NF1基因突变所致,神经纤维瘤蛋白是NF1基因编码蛋白,是一种肿瘤抑制蛋白,可抑制细胞的过度生长。NF1基因突变不仅可导致细胞过度生长,还可增加良性及恶性肿瘤的发生风险。本研究中,我们通过基因突变分析,确定中国东北地区一个伴有先天性白内障的Ⅰ型神经纤维瘤家系NF1基因的突变位点。方法:通过聚合酶链反应(PCR)和NF1基因直接测序分析对家系中的3名患者及2名健康成员进行基因突变检测,以确定其突变位点。结果:此家系呈常染色体显性遗传。通过基因序列分析发现NF1基因第1140密码子第二个碱基呈杂合子点突变C→G,导致一个无义突变S1140X,家系中健康成员和正常对照未检测到此突变存在。结论:通过NF1基因测序分析,我们发现NF1基因的S1140X突变是引起该家系NF1疾病的致病原因,该突变导致NF1基因终止密码提前,神经纤维瘤素蛋白截短。本研究丰富了我国关于Ⅰ型神经纤维瘤病在眼科的临床表现。Objective： Neurofibromatosis type 1 is a common autosomal dominant that primarily involves the skin and the nervous system. It has variable expressivity and is characterised by cafe au lait spots, cutaneous neurofibromas, iris Lisch nodules and axillxry and inguinal freckling. NF1 is caused by a mutation in the NFlgene. Neurofibromin, the protein products of the normal nfl gene, acts as a tumor suppressor and limits cell growth. Mutation in thes gone leads to yell overgrowth and an increased risk of developing benign and malig- nant tumor. In this study, we present a clinical and molecular study of a northeastern Chinese family with Neurofibromatosis type I . Methods： Three patients, two non-cartier relatives of the family with NF1 were enrolled in this study. In addition to ophthalmologic ex- aminations, PCR amplification and nucleotide sequencing of all coding exons of the NF1 gene were carried out. Results： A nonsense mu- tation S1140X in the NF1 gene was identifed. This mutation truncates the NF1 protein by 3419 amino acid residues at the C-terminus, but not present in unaffected individuals in the family and healthy controls. Conclusion： Through the DNA sequencing for whole coding region of NF1, we identified a mutation S1304X in the NF1 gene that caused Neurofibromatosis type I in this family. This mutation lead to premature-stop codon and tnmcated the NF1 protein. This study enriched the clinical features of Neurofibromatosis type 1 in ophthal- mology.

关 键 词：I型神经纤维瘤病 基因突变 分析 

分 类 号：R394.3[医药卫生—医学遗传学]