title: Mutation analysis of connexin 50 gene among Iranian families with autosomal dominant cataracts.
abstract: OBJECTIVE
  Childhood cataract is a genetically heterogeneous eye disorder that results in visual impairment. The aim of this study was to identify the genetic mutations of connexin 50 gene among Iranian families suffered from autosomal dominant congenital cataracts (ADCC).
  
  
  METHODS
  Families, having at least two members with bilateral familial congenital cataract, were selected for the study. Probands were evaluated by detailed ophthalmologist's examination, and the pedigree analysis was performed. PCR amplifications were performed corresponding to coding region and intron-exon boundaries ofGJA8, a candidate gene responsible for ADCC. PCR products were subjected to bidirectional sequencing, and the co-segregation of identified mutations was examined and finally, the impact of identified mutations on biological functions ofGJA8was predicted by in silico examination.
  
  
  RESULTS
  Three different genetic alterations, including c.130G>A (p.V44M), c.301G>T (p.R101L) and c.134G>T (p.W45L) inGJA8gene were detected among three probands. Two identified mutations, W45L and V44M have been already reported, while the R101L is a novel mutation and its co-segregation was examined. This mutation was exclusively detected in the ADCC and could not be found among the healthy control group. The result of bioinformatic studies of R101L mutation predicted that this amino acid substitution withinGJA8could be a disease-afflicting mutation due to its potential effect on the protein structure and biological function.
  
  
  CONCLUSIONS
  Our results suggest that mutations of lens connexin genes such asGJA8gene could be one of the major mechanisms of cataract development, at least in a significant proportion of Iranian patients with ADCC.
authors.affiliation: Farabi Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Mohebi
authors.affiliation: Farabi Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Chenari
authors.affiliation: Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Akbari
authors.affiliation: Farabi Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Ghassemi
authors.affiliation: Farabi Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehran
authors.initials: M
authors.lastname: Zarei-Ghanavati
authors.affiliation: Farabi Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ghasem
authors.initials: G
authors.lastname: Fakhraie
authors.affiliation: Department of Molecular Biology and Genetics, Islamic Azad University, Bushehr Branch, Bushehr, Iran.
authors.forename: Nahid
authors.initials: N
authors.lastname: Babaie
authors.affiliation: Department of Molecular Biology and Genetics, Islamic Azad University, Bushehr Branch, Bushehr, Iran; Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mansour
authors.initials: M
authors.lastname: Heidari
keywords: Cataract; Congenital; Connexine 50 gene; GJA8; Mutation