PAX6基因IVS10＋1G》A新突变导致中国东北地区一先天性无虹膜家系  

A novel mutation of the PAX6 gene in a Chinese family with aniridia

作　　者：康杨[1] 原慧萍[2] 李雪[1] 李庆军[1] 吴琼[1] 胡琦[1] 

机构地区：[1]哈尔滨医科大学附属一院眼科视光中心,150001 [2]哈尔滨医科大学附属一院附属二院眼科,150001

出　　处：《中华医学遗传学杂志》2010年第4期376-380,共5页Chinese Journal of Medical Genetics

基　　金：基金项目：黑龙江省教育厅科学技术研究项目（11521159）

摘　　要：目的 人类配对盒基因（paired-box gene 6,PAX6）基因编码一个转录因子,其异常会导致眼部虹膜组织发育异常,产生罕见的家族性先天性无虹膜疾病.通过分子遗传学分析,确定中国东北地区一个先天性无虹膜家系PAX6基因的突变位点.方法 对一个先天性无虹膜家系所有成员进行全面的眼部检查,采集该家系的2例患者和5名健康成员和100名正常对照者的外周静脉血,提取基因组DNA,应用聚合酶链反应扩增PAX6基因的第4至13外显子,直接测序法确定致病的基因突变,用单链构像多态性方法对结果进行验证并对对照者进行筛选.结果 该家系为位于PAX6基因第10外显子和第10内含子交界处的杂合突变（IVS10＋1G＞A）,致使DNA剪接异常,使得PAX6基因的单倍剂量不足.结论 该家系先天性无虹膜是常染色体显性遗传,PAX6基因是中国东北地区先天性无虹膜的致病基因,PAX6基因在眼部发育中具有重要作用,并发现了PAX6基因一个新的突变位点.Objective The PAX6 gene encodes a transcriptional regulator involved in oculogenesis and other developmental processes such as aniridia, a congenital condition characterized by the underdevelopment of the iris of eyes. The function of the PAX6 gene in these two conditions is still poorly defined. The purpose of this study is to identify the mutation of the PAX6 gene in a Chinese family with aniridia. Methods Two aniridia patients collected from the family underwent full ophthalmologic examination. Genomic DNA was prepared from venous leukocytes of the two patients and five healthy individuals in the family, and 100 unrelated healthy controls. Exons 4-13 and their immediate flanking sequences of the PAX6 gene was analyzed by PCR amplification, direct sequencing, and single-strand conformation polymorphism（SSCP）. Results The sequencing result revealed a novel PAX6 mutation in the two patients. It was a heterozygous mutation （IVS10＋1G＞ A） at the boundary of exon 10 and intron 10.The mutation was also detected by SSCP analysis. It was not detected in the healthy relatives and unrelated controls. Conclusion Aniridia is an autosomal dominant inheritable disease. A novel PAX6 gene mutation has been identified in the Northeastern Chinese family with aniridia. The genetic analysis suggested that this novel mutation in the PAX6 gene is capable of causing the classic aniridia phenotype.

关 键 词：PAX6基因 先天性无虹膜 剪接异常 

分 类 号：R773.1[医药卫生—眼科]