原纤维蛋白1基因新突变导致单纯性晶状体异位

• 作 者: 睢瑞芳 魏洪斌 赵家良 胡韶毅 王波 黄尚志 董敏
• 机 构: 中国协和医科大学中国医学科学院北京协和医院眼科眼科研究中心,解放军第二五二医院眼科,中国协和医科大学中国医学科学院北京协和医院眼科眼科研究中心,中国医学科学院基础研究所中国协和医科大学基础医学院,解放
• 出 处: 中华眼科杂志
• 发表日期: 2004年12期
• 关键词: 原纤维蛋白1 晶体异位 突变 基因

目的　研究我国单纯性晶状体异位家系的致病基因 ,并确定基因突变。方法　对单纯性晶状体异位一家系进行临床研究和系谱分析。采集家系中 7例患者和 3例健康成员的静脉血 ,提取基因组DNA。通过连锁分析确定致病基因的染色体位点后 ,应用聚合酶链反应 (PCR)扩增原纤维蛋白(FBN) 1基因外显子 ,直接测序确定致病的基因突变。采用PCR和限制性内切酶法进行群体分析。结果　单纯性晶状体异位患者的FBN1基因外显子 6发生了错义突变 ,cDNA 6 4 0位的鸟嘌呤被腺嘌呤取代 (G6 4 0A) ;对应的甘氨酸改变为丝氨酸 (G2 14S)。突变后EagⅠ内切酶位点消失。家系中健康成员和5 0名正常人均未发现该突变。结论　FBN1基因新突变G6 4 0A (G2 14S)是该家系单纯性晶状体异位的致病基因突变。

Objective To study the causative genes of simple lens ectopic families in China and determine the gene mutation. Methods The clinical study and pedigree analysis of a family of simple lens ectopic. Venous blood was collected from 7 patients in the pedigree and 3 healthy controls to extract genomic DNA. After confirming the chromosomal location of the causative gene by linkage analysis, the exon of fibrillin (FBN) 1 gene was amplified by polymerase chain reaction (PCR) and sequenced to determine the causative gene mutation. Population analysis was performed using PCR and restriction endonuclease assays. Results A mutation in exon 6 of FBN1 gene was found in patients with simple lens ectopic. The guanine in cDNA 640 was substituted by adenine (G6 40A) and the corresponding glycine was changed to serine (G2 14S). The mutated Eag I endonuclease site disappeared. The family members and healthy members of 50 normal subjects did not find the mutation. Conclusion The novel FBG1 gene mutation G640A (G214S) is a causative gene mutation of the simple lens ectopic of this family.