论文部分内容阅读
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: Type I neurofibromatosis is a common autosomal dominant genetic disorder that mainly affects the skin and nervous system. Its clinical manifestations are diverse and are characterized primarily by “coffee milk spots”, cutaneous neurofibromas, iris Lisch nodules, armpits and groin spots, type I neurofibromatosis caused by a mutation in the NF1 gene, neurofibromin protein The NF1 gene encodes a protein that is a tumor suppressor protein that inhibits cell overgrowth. NF1 gene mutations not only lead to cell overgrowth, but also increase the risk of benign and malignant tumors. In this study, we determined the mutation site of the NF1 gene in a family of neurofibromatosis type I with congenital cataract in northeastern China by gene mutation analysis. METHODS: Three patients in the pedigree and two healthy individuals were genotyped by polymerase chain reaction (PCR) and direct NF1 gene sequencing to determine their mutation sites. Results: The family was autosomal dominant. Gene sequence analysis revealed that the second base of codon 1140 of NF1 gene was a heterozygous point mutation C → G, resulting in a nonsense mutation S1140X, which was not detected in healthy members of the pedigree and normal controls. CONCLUSIONS: Through NF1 gene sequencing analysis, we found that S1140X mutation of NF1 gene is the causative agent of NF1 in this pedigree. This mutation leads to the early termination of NF1 gene code and the truncation of neurofibromin protein. This study enriched the clinical manifestations of type I neurofibromatosis in ophthalmology in China.