title: A novel mutation of COL2A1 resulting in dominantly inherited rhegmatogenous retinal detachment.
abstract: OBJECTIVE
  To determine the molecular defect in a family with autosomal dominant rhegmatogenous retinal detachment (DRRD), and to investigate missplicing as a possible phenotypic modifier of mutations in COL2A1.
  
  
  METHODS
  Clinical examination of the family and linkage analysis using markers flanking COL2A1 and COL11A1, the known loci for Stickler syndrome; mutation screening of COL2A1; construction of splicing reporter minigenes and transfection into cultured cells; and RT-PCR analysis of reporter specific transcripts.
  
  
  RESULTS
  A family with DRRD showed no systemic clinical signs (skeletal, orofacial, or auditory) usually associated with Stickler syndrome. Linkage analysis excluded COL11A1 as the disease locus but could not exclude COL2A1. Mutation screening of COL2A1 identified a novel G118R mutation in type II collagen. Transfection of minigenes carrying mutations associated with DRRD (G118R, R453X, and L467F) into cultured cells detected no missplicing of mRNA from mutant constructs.
  
  
  CONCLUSIONS
  Mutations outside the alternatively spliced exon 2 region of COL2A1 can also result in an ocular only phenotype. There was no evidence that missplicing modifies the phenotype of these mutations, suggesting that the minimal or absent systemic features demonstrated by the G118R and L467F mutations are the result of the biophysical changes imparted on the collagen molecule.
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Richards
authors.forename: Sarah
authors.initials: S
authors.lastname: Meredith
authors.forename: Arabella
authors.initials: A
authors.lastname: Poulson
authors.forename: Philip
authors.initials: P
authors.lastname: Bearcroft
authors.forename: Graeme
authors.initials: G
authors.lastname: Crossland
authors.forename: David M
authors.initials: DM
authors.lastname: Baguley
authors.forename: John D
authors.initials: JD
authors.lastname: Scott
authors.forename: Martin P
authors.initials: MP
authors.lastname: Snead
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D002478:Cells, Cultured; D024043:Collagen Type II / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D012163:Retinal Detachment / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II; D012333:RNA, Messenger