Ying Xiao1, Xiangqin Liu2,3, Chen Yang2, Liping Liu1, Xiaoxin Guo2, Qi Wang1, Bo Gong2,3. 1. 1 Department of Ophthalmology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China. 2. 2 The Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. 3. 3 Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
Abstract
Purpose: Congenital aniridia is a kind of panocular disorder characterized by the absence of the iris in both eyes. Paired box 6 (PAX6) gene mutations have been identified as the most common cause of congenital aniridia. The aim of this study was to reveal the genetic defect in PAX6 in a Chinese family with congenital aniridia. Methods: Twelve individuals from a three-generation Chinese family were recruited. All the family members underwent comprehensive ophthalmologic examinations. The entire coding region of PAX6 was amplified by polymerase chain reaction, followed by direct Sanger sequencing. Possible structural and functional changes of protein were predicted by bioinformatic analysis using SIFT and Polyohen-2. Results: Among all the 12 members, four were clinically diagnosed with congenital aniridia. A novel heterozygous mutation c.275G>A (p.R92Q) in exon 6 of PAX6 was identified in all the patients, but not in the unaffected individuals or 1186 healthy subjects. This missense mutation is a G-A transition, converting Arginine (R) to Glutamine (Q) at amino acid 92. The substitution of amino acid in the PAX6 protein changed the local charge density and was predicted to damage the normal protein function. Conclusions: Our study identified a novel mutation of PAX6 responsible for congenital aniridia in a Chinese family, which may contribute to understanding the molecular basis and clinical diagnosis of congenital aniridia.
Purpose: Congenital aniridia is a kind of panocular disorder characterized by the absence of the iris in both eyes. Paired box 6 (PAX6) gene mutations have been identified as the most common cause of congenital aniridia. The aim of this study was to reveal the genetic defect in PAX6 in a Chinese family with congenital aniridia. Methods: Twelve individuals from a three-generation Chinese family were recruited. All the family members underwent comprehensive ophthalmologic examinations. The entire coding region of PAX6 was amplified by polymerase chain reaction, followed by direct Sanger sequencing. Possible structural and functional changes of protein were predicted by bioinformatic analysis using SIFT and Polyohen-2. Results: Among all the 12 members, four were clinically diagnosed with congenital aniridia. A novel heterozygous mutation c.275G>A (p.R92Q) in exon 6 of PAX6 was identified in all the patients, but not in the unaffected individuals or 1186 healthy subjects. This missense mutation is a G-A transition, converting Arginine (R) to Glutamine (Q) at amino acid 92. The substitution of amino acid in the PAX6 protein changed the local charge density and was predicted to damage the normal protein function. Conclusions: Our study identified a novel mutation of PAX6 responsible for congenital aniridia in a Chinese family, which may contribute to understanding the molecular basis and clinical diagnosis of congenital aniridia.