title: Autosomal recessive congenital cataract linked to EPHA2 in a consanguineous Pakistani family.
abstract: OBJECTIVE
  To investigate the genetic basis of autosomal recessive congenital cataracts in a consanguineous Pakistani family.
  
  
  METHODS
  All affected individuals underwent a detailed ophthalmological and clinical examination. Blood samples were collected and genomic DNAs were extracted. A genome-wide scan was performed with polymorphic microsatellite markers. Logarithm of odds (LOD) scores were calculated, and Eph-receptor type-A2 (EPHA2), residing in the critical interval, was sequenced bidirectionally.
  
  
  RESULTS
  The clinical and ophthalmological examinations suggested that all affected individuals have nuclear cataracts. Genome-wide linkage analyses localized the critical interval to a 20.78 cM (15.08 Mb) interval on chromosome 1p, with a maximum two-point LOD score of 5.21 at theta=0. Sequencing of EPHA2 residing in the critical interval identified a missense mutation: c.2353G>A, which results in an alanine to threonine substitution (p.A785T).
  
  
  CONCLUSIONS
  Here, we report for the first time a missense mutation in EPHA2 associated with autosomal recessive congenital cataracts.
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Haiba
authors.initials: H
authors.lastname: Kaul
authors.forename: S Amer
authors.initials: SA
authors.lastname: Riazuddin
authors.forename: Mariam
authors.initials: M
authors.lastname: Shahid
authors.forename: Samra
authors.initials: S
authors.lastname: Kousar
authors.forename: Nadeem H
authors.initials: NH
authors.lastname: Butt
authors.forename: Ahmad U
authors.initials: AU
authors.lastname: Zafar
authors.forename: Shaheen N
authors.initials: SN
authors.lastname: Khan
authors.forename: Tayyab
authors.initials: T
authors.lastname: Husnain
authors.forename: Javed
authors.initials: J
authors.lastname: Akram
authors.forename: J Fielding
authors.initials: JF
authors.lastname: Hejtmancik
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002386:Cataract / Q000151:congenital* / Q000201:enzymology / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003241:Consanguinity; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D010154:Pakistan; D010375:Pedigree; D036104:Receptor, EphA2 / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D036104:Receptor, EphA2