Molecular Genetics Of A Chinese Family With Aniridia Complicated With Nystagmus

Congenital coloboma of iris（Aniridia,referred to as aniridia） is a rare developmental disease involving the the eyes, the main characteristic is showed varying degrees of ocular tissue abnormalities,such as nystagmus, amblyopia, buphthalmos, and cataract. A population frequency is about 1 in 60,000–100,000. The disease was first reported by Barrata in1821.Paired box factor 6, PAX6 gene（OMIM 607108, Gen Bank M93650） was first find to related of aniridia disease gene,located in chromosome 11p13, spans 22 kb and consists of 14 exons and 13 introns.the PAX6 is involved in growth and development process of a variety of tissues and organs,and in responsible for the regulation, including the ocular surface tissue, olfactory bulb, neural tube, gut and pancreas. When the gene is abnormal, it will cause a corresponding clinical manifestations, such as aniridia, corneal opacity, keratitis, cataract,glaucoma, crystal ectopic or absent, ciliary body hypoplasia, foveal hypoplasia, strabismus,nystagmus, Peter’s abnomal, optic defects and so on.In this study,the initial diagnosis in the family for all patients with congenital aniridia associated with nystagmus, clinical phenotype is slightly different. We hope that through the analysis of clinical and molecular genetics, pathogenic gene and mutation detection in the family,explore the molecular genetics mechanism of congenital PAX6 gene mutation which caused aniridia and nystagmus.Purpose: The purpose of this study was to identify the clinical features and mutations in the PAX6 in a Chinese family with congenital aniridia and nystagmus.Methods: Complete history-taking and ophthalmologic examinations were performed on five patients and three unaffected individuals in this three-generation family.All exons of PAX6 were amplified by polymerase chain reaction（PCR）, sequenced and compared with a reference database.Results:The propositus presented with nystagmus and iris anomalies.His father was diagnosed with nystagmus,iris anomalies and aphakic eye at birth while his aunt and cousin presented with congenital aniridia, nystagmus and cataract. Phenotype of the rest members in the family is normal. All exons of PAX6 of the affected and normal individuals included in this studywere analyzed by direct sequencing. A heterozygous mutation, c.393₃96del TAGC, was identified. The abnormality corresponding to exon 7 was detected in 5 aniridia patients, but was not detected in the 3 unaffected family members.The novel mutation c.393₃96del TAGC occured co-segregation inthe family which may account for the pathogenesis of the congenital aniridia and nystagmus in this pedigree.Conclusion: A novel mutation c.393₃96del TAGC in exon 7 of PAX6 was identified in all affected individuals. This mutation was first reported in the world up to date which enriched the database of human PAX6 mutation.