Liu Xiaoqi, Wu Yaqi, Miao Zequn, Zhang Houbin, Gong Bo, Zhu Xianjun, Huang Lulin, Shi Yi, Hao Fang, Ma Shi, Lin He, Wang Lejin, Yang Zhenglin
a Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine , University of Electronic Science and Technology of China , Chengdu , China.
b Center of Information in Biomedicine , University of Electronic Science and Technology of China , Chengdu , China.
Ophthalmic Genet. 2018 Aug;39(4):428-436. doi: 10.1080/13816810.2018.1466336. Epub 2018 Jun 14.
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.
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.
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.
A novel deletion mutation was identified within the PAX6 downstream region that results in congenital aniridia.
先天性无虹膜是一种严重的双眼全眼球视觉障碍，是常染色体显性遗传的眼部异常。已证明配对盒6基因（PAX6）突变是大多数先天性无虹膜患者的病因。本研究的目的是报告一个先天性无虹膜中国家系的临床特征，并筛查先天性无虹膜的新基因突变。
一个三代家系的所有成员均接受了全面的眼科检查，其25名成员中有8名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，并对该家系进行连锁分析。通过直接DNA测序确认突变。
使用Illumina公司的Human Linkage-12珠芯片微阵列（包含6090个单核苷酸多态性）进行全基因组扫描，对数优势（LOD）评分值显示，11号染色体上rs1389423至rs910090之间的区间呈现强连锁。在所有患病家庭成员中鉴定出PAX6下游区域内一个新的杂合469 kb缺失突变（chr11:31189937-31659379），未患病家庭成员或2000名种族匹配的对照中未发现该突变。
在PAX6下游区域鉴定出一个导致先天性无虹膜的新缺失突变。
