Mutation analysis of paired box 6 gene in inherited aniridia in northern China
Mutation analysis of paired box 6 gene in inherited aniridia in northern China
复制标题
中国北方遗传性无虹膜配对盒6基因突变分析
作者：
Chen, Peng;Zang, Xinjie;Sun, Dapeng;Wang, Ye;Wang, Yao;Zhao, Xiaowen;Zhang, Mohan;Xie, Lixin
目的无虹膜是一种表型和遗传异质性的疾病。本研究旨在总结中国北部两个三代中国人无虹膜家系中PAX6基因的表型，并探讨其潜在的遗传原因。方法收集眼科检查患者详细的家族史和临床资料。用聚合酶链式反应扩增PAX6基因的所有外显子和侧翼内含子序列，并用DNA直接测序法筛选突变。用单倍型方法对突变序列进行确认。用实时定量聚合酶链式反应检测无虹膜患者和正常家庭成员的PAX6信使核糖核酸(MRNA)水平。结果两家系先证者及其他患者均伴有或不伴有先天性白内障的虹膜缺乏症。在家系-1中发现了外显子5(c.112delC，p.Arg38GlyfsX16)的PAX6杂合性突变，该突变被预测为产生移码并产生提前终止密码子。在家系2中发现了外显子7(c.362C>；T，p.Ser121Leu)的PAX6杂合性突变。每个突变都与家族中受影响的个体共聚，而在未受影响的家庭成员和200名无血缘关系的正常对照中不存在。在家族1中，无虹膜患者的PAX6信使核糖核酸水平比未受影响的家庭成员低约50%。结论PAX6基因缺失突变(c.112delC)首次发现于无虹膜、先天性进行性白内障、发育迟缓或尺骨缺失的家系。PAX6基因的突变(c.362C>；T，p.Ser121Leu)首次在1例先天性上睑下垂的无虹膜患者中被发现。我们总结了患者的不同表型，扩大了不同种族背景下无虹膜的表型谱。
Purpose Aniridia is phenotypically and genetically heterogeneous. This study is to summarize the phenotypes and identify the underlying genetic cause of the paired box 6 (PAX6) gene responsible for aniridia in two three-generation Chinese families in northern China. Methods A detailed family history and clinical data were collected from patients during an ophthalmologic examination. All exons and flanking intronic sequences of the PAX6 gene were amplified with PCR and screened for mutation with direct DNA sequencing. Haplotyping was used to confirm the mutation sequence. Real-time PCR was used to determine the PAX6 messenger ribonucleic acid(mRNA) level in patients with aniridia and in unaffected family members. Results The probands and other patients in the two families were affected with aniridia accompanied with or without congenital cataract. A heterozygous PAX6 mutation in exon 5 (c.112delC, p.Arg38GlyfsX16) was identified in FAMILY-1, which was predicted to generate a frameshift and created a premature termination codon. A heterozygous PAX6 mutation in exon 7 (c.362C>T, p.Ser121Leu) was identified in FAMILY-2. Each mutation cosegregated with the affected individuals in the family and did not exist in unaffected family members and 200 unrelated normal controls. The PAX6 messenger ribonucleic acid level was about 50% lower in patients with aniridia than in unaffected family members in FAMILY-1. Conclusions The deletion mutation (c.112delC) in the PAX6 gene was first identified in a Chinese family with aniridia, congenital progressive cataract, developmental delay, or the absence of ulna. The mutation (c.362C>T, p.Ser121Leu) in the PAX6 gene was first identified in a patient with aniridia with congenital ptosis. We summarized the variable phenotypes among the patients, which expanded the phenotypic spectrum of aniridia in a different ethnic background.
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影响因子：
2.2
作者：
E. Redeker;Annette S.H. de Visser;A. Bergen;M. Mannens
通讯作者：
E. Redeker;Annette S.H. de Visser;A. Bergen;M. Mannens
DOI：
10.3760/cma.j.issn.0412-4081.2009.10.015
发表时间：
2009-10
期刊：
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology
影响因子：
--
作者：
Pengcheng Li;Q. Yao;X. Ren;Ming-Chang Zhang;Hui Li;Jing-Yu Liu;Shuang-yan Sheng;Qing Wang;
通讯作者：
Pengcheng Li;Q. Yao;X. Ren;Ming-Chang Zhang;Hui Li;Jing-Yu Liu;Shuang-yan Sheng;Qing Wang;
影响因子：
4.5
作者：
H. Yepiskoposyan;Florian Aeschimann;D. Nilsson;M. Okoniewski;O. Mühlemann
通讯作者：
H. Yepiskoposyan;Florian Aeschimann;D. Nilsson;M. Okoniewski;O. Mühlemann
DOI：
--
发表时间：
2008-04
期刊：
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics
影响因子：
--
作者：
Y. Kang;H. Yuan;Yuan-yuan Li
通讯作者：
Y. Kang;H. Yuan;Yuan-yuan Li
DOI：
10.3760/cma.j.issn.1003-9406.2009.05.015
发表时间：
2009-10
期刊：
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics
影响因子：
--
作者：
Ying Lin;Jing Li;Yang Yang-Yang;Jiyun Yang;Ben Zhang;Xin-zhi Tang;Xiaoqui Liu;Fang Lu;Zheng-lin Y
通讯作者：
Ying Lin;Jing Li;Yang Yang-Yang;Jiyun Yang;Ben Zhang;Xin-zhi Tang;Xiaoqui Liu;Fang Lu;Zheng-lin Y