A novel deletion downstream of the PAX6 gene identified in a Chinese family with congenital aniridia
A novel deletion downstream of the PAX6 gene identified in a Chinese family with congenital aniridia
复制标题
在一个先天性无虹膜的中国家族中发现了 PAX6 基因下游的新缺失
DOI：
10.1080/13816810.2018.1466336
复制
发表时间：
2018-01-01
影响因子：
1.2
通讯作者：
Yang, Zhenglin
中科院分区：
文献类型：
--
作者：
Liu, Xiaoqi;Wu, Yaqi;Yang, Zhenglin
目的：先天性无虹膜是一种严重的双眼全眼视觉障碍，是一种常染色体显性遗传性眼畸形。配对盒6基因（PAX 6）的突变已被证明是大多数患者先天性无虹膜的原因。本研究的目的是报告一个先天性无虹膜家系的临床特点，并筛选新的基因突变的先天性aniridia.Methods：所有成员的三代人进行全面的眼科检查，其25名成员中的8个被诊断为先天性无虹膜。对先证者进行外显子组测序和全基因组测序，并对家系进行连锁分析。结果：采用Illumina公司的Human Linkage-12微珠芯片（含6090个SNPs）全基因组扫描，LOD评分值显示11号染色体上rs 1389423 ~ rs 910090之间存在较强的连锁关系。一个新的杂合469 kb的PAX 6（Chr 11：31189937-31659379）的下游区域内的缺失突变被确定在所有受影响的家庭成员，但没有在未受影响的家庭成员或2000种族匹配controls.Conclusion：一个新的缺失突变被确定在PAX 6的下游区域内，导致先天性无虹膜。
Purpose: Congenital aniridia, a severe bilateral panocular visual disorder, is an autosomal dominantly inherited eye anomaly. Mutations in the paired box 6 gene (PAX6) have been shown to be responsible for congenital aniridia in most patients. The purpose of the present study was to report clinical features of a Chinese family with congenital aniridia and to screen novel genetic mutations for congenital aniridia.Methods: All members of a three-generation family underwent comprehensive ophthalmic examination, and 8 of its 25 members were diagnosed with congenital aniridia. The proband was analyzed by exome sequencing and whole genome sequencing, and linkage analysis was performed for the family. The mutation was confirmed by direct DNA sequencing.Results: Using Illumina's Human Linkage-12 beadchip microarray (including 6090 SNPs) whole genome scan, the LOD score value showed that the interval on chromosome 11 between rs1389423 to rs910090 exhibited a strong linkage. A novel heterozygous 469 kb deletion mutation within the downstream region of PAX6 (chr11:31189937-31659379) was identified in all affected family members, but not in unaffected family members or 2000 ethnically matched controls.Conclusion: A novel deletion mutation was identified within the PAX6 downstream region that results in congenital aniridia.