Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
National Clinical Research Center for Eye Diseases, Shanghai, China.
BMC Ophthalmol. 2023 Sep 26;23(1):393. doi: 10.1186/s12886-023-03147-1.
To identify the disease-causing gene in a Chinese family affected with congenital aniridia.
Patients underwent systematic ophthalmic examinations such as anterior segment photography, fundus photography, optical coherence tomography, and fundus fluorescein angiography. The proband was screened for pathogenic variants by whole exome sequencing (WES) and copy number variant (CNV) analysis. Real-time quantitative PCR (RT-qPCR) was applied to confirm the CNV results. Breakpoints were identified by long-range PCR followed by Sanger sequencing.
All seven members of this Chinese family, including four patients and three normal individuals, were recruited for this study. All patients showed bilateral congenital aniridia with nystagmus, except the son of the proband, who presented with bilateral partial coloboma of the iris. A novel heterozygous deletion (chr11:31,139,019-31,655,997) containing the 3' regulatory enhancers of the PAX6 gene was detected in this family. We also reviewed the reported microdeletions downstream of PAX6 in patients with aniridia.
We identified a novel microdeletion, 517 kb in size located about 133 kb downstream of the PAX6 gene, responsible for congenital aniridia in this Chinese family, which expands the spectrum of aniridia-associated mutations in PAX6.
鉴定一个受先天性无虹膜症影响的中国家庭的致病基因。
对患者进行系统的眼科检查，包括眼前节照相、眼底照相、光学相干断层扫描和眼底荧光血管造影。对先证者进行全外显子组测序（WES）和拷贝数变异（CNV）分析以筛选致病变异。实时定量 PCR（RT-qPCR）用于确认 CNV 结果。通过长距离 PCR 结合 Sanger 测序确定断点。
本研究共纳入该中国家庭的七名成员，包括四名患者和三名正常个体。所有患者均表现为双侧先天性无虹膜伴眼球震颤，除先证者的儿子外，他还表现为双侧部分虹膜缺损。该家系中发现了一个新的杂合性缺失（chr11:31,139,019-31,655,997），包含 PAX6 基因的 3'调控增强子。我们还回顾了报道的 PAX6 下游微缺失患者的情况。
我们鉴定了一个新的微缺失，大小为 517kb，位于 PAX6 基因下游约 133kb 处，导致该中国家系的先天性无虹膜症，扩大了 PAX6 相关突变导致无虹膜症的谱。
