title: Investigation of crystallin genes in familial cataract, and report of two disease associated mutations.
abstract: OBJECTIVE
  Mutations of seven crystallin genes have been shown to cause familial cataract. The authors aimed to identify disease causing crystallin mutations in paediatric cataract families from south eastern Australia.
  
  
  METHODS
  38 families with autosomal dominant or recessive paediatric cataract were examined. Three large families were studied by linkage analysis. Candidate genes at regions providing significant LOD scores were sequenced. Single stranded conformational polymorphism (SSCP) analysis was used to screen five crystallin genes in the probands, followed by direct sequencing of observed electrophoretic shifts. Mutations predicted to affect the coding sequence were subsequently investigated in the entire pedigree.
  
  
  RESULTS
  A LOD score of 3.72 was obtained at the gamma-crystallin locus in one pedigree. Sequencing revealed a P23T mutation of CRYGD, found to segregate with disease. A splice site mutation at the first base of intron 3 of the CRYBA1/A3 gene segregating with disease was identified by SSCP in another large family. Five polymorphisms were also detected.
  
  
  CONCLUSIONS
  Although mutations in the five crystallin genes comprehensively screened in this study account for 38% of paediatric cataract mutations in the literature, only two causative mutations were detected in 38 pedigrees, suggesting that crystallin mutations are a relatively rare cause of the cataract phenotype in this population.
authors.affiliation: Menzies Centre for Population Health Research, University of Tasmania, Hobart, Australia.
authors.forename: K P
authors.initials: KP
authors.lastname: Burdon
authors.forename: M G
authors.initials: MG
authors.lastname: Wirth
authors.forename: D A
authors.initials: DA
authors.lastname: Mackey
authors.forename: I M
authors.initials: IM
authors.lastname: Russell-Eggitt
authors.forename: J E
authors.initials: JE
authors.lastname: Craig
authors.forename: J E
authors.initials: JE
authors.lastname: Elder
authors.forename: J L
authors.initials: JL
authors.lastname: Dickinson
authors.forename: M M
authors.initials: MM
authors.lastname: Sale
mesh_terms: D002386:Cataract / Q000151:congenital / Q000235:genetics*; D002648:Child; D003459:Crystallins / Q000235:genetics*; D015785:Eye Diseases, Hereditary / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008297:Male; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D003459:Crystallins