title: Mutations in the EPHA2 gene are a major contributor to inherited cataracts in South-Eastern Australia.
abstract: Congenital cataract is the most common cause of treatable visual impairment in children worldwide. Mutations in many different genes lead to congenital cataract. Recently, mutations in the receptor tyrosine kinase gene, EPHA2, have been found to cause congenital cataract in six different families. Although these findings have established EPHA2 as a causative gene, the total contribution of mutations in this gene to congenital cataract is unknown. In this study, for the first time, a population-based approach was used to investigate the frequency of disease causing mutations in the EPHA2 gene in inherited cataract cases in South-Eastern Australia. A cohort of 84 familial congenital or juvenile cataract index cases was screened for mutations in the EPHA2 gene by direct sequencing. Novel changes were assessed for segregation with the disease within the family and in unrelated controls. Microsatellite marker analysis was performed to establish any relationship between families carrying the same mutation. We report a novel congenital cataract causing mutation c.1751C>T in the EPHA2 gene and the previously reported splice mutation c.2826-9G>A in two new families. Additionally, we report a rare variant rs139787163 potentially associated with increased susceptibility to cataract. Thus mutations in EPHA2 account for 4.7% of inherited cataract cases in South-Eastern Australia. Interestingly, the identified rare variant provides a link between congenital and age-related cataract.
authors.affiliation: Department of Ophthalmology, Flinders University, Bedford Park, SA, Australia.
authors.forename: Alpana
authors.initials: A
authors.lastname: Dave
authors.forename: Kate
authors.initials: K
authors.lastname: Laurie
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Staffieri
authors.forename: Deepa
authors.initials: D
authors.lastname: Taranath
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
authors.forename: Shiwani
authors.initials: S
authors.lastname: Sharma
mesh_terms: D001315:Australia / Q000453:epidemiology; D002386:Cataract / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D005190:Family; D005260:Female; D005787:Gene Frequency; D030342:Genetic Diseases, Inborn / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D036104:Receptor, EphA2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D036104:Receptor, EphA2