Aniridia And Congenital Progressive Cataract In A Chinese Family Is Associated With A Recurrent PAX6Mutation

Purpose:Aniridia is a phenotyically and genetically heterogeneous disease. This research is to summarize the phenotypes and detect the genetic abnormality resulting in aniridia and congenital progressive cataract in a three generation Chinese family.Methods:Through a number of ophthalmologic examination (including visual acuity, slit-lamp examination, tonometer, ultrasonic A/B scan, optical coherence tomography, keratometry, and corneal topography), we collected a detailed family history and clinical data from affected and unaffected individuals in the family. By polymerase chain reaction (PCR) and direct DNA sequencing, all exons and flanking intronic sequences of the paired box6(PAX6) gene were amplified and screened for mutation. Bioinformatics analysis was used for analyzing the structure and function of the mutant PAX6.Results:Shared manifestations of complete aniridia, congenital cataract and thickened cornea was detected in all the six patient, and wide-ranging phenotypic variability was observed in corneal pannus, corneal curvature, corneal vascularization, cataract subtype, ectopia lentis, optic disc anomalies, nystagmus, ptosis, strabismus, glaucoma, and axial length. Through sequencing the candidate gene, we detected a heterozygous transition in the coding region of PAX6which brings about the substitution of arginine codon for a termination codon (p.R103X). The PAX6c.307C>T mutation co-segregated with the patients in the family. Based on computational analysis, the mutation was supposed to be the cause of the structural and functional changes.Conclusions:We summarized various phenotypes in an aniridia and congenital progressive cataract family and identified a recurrent PAX6c.307C>T mutation among the patients. Our study expanded the phenotypic spectrum of aniridia in a different ethnic background.