title: A new VCAN/versican splice acceptor site mutation in a French Wagner family associated with vascular and inflammatory ocular features.
abstract: OBJECTIVE
  To detail the highly variable ocular phenotypes of a French family affected with an autosomal dominantly inherited vitreoretinopathy and to identify the disease gene.
  
  
  METHODS
  Sixteen family members with ten affected individuals underwent detailed ophthalmic evaluation. Genetic linkage analysis and gene screening were undertaken for genes known to be involved in degenerative and exudative vitreoretinopathies. Qualitative reverse transcriptase-PCR analysis of the versiscan (VCAN) transcripts was performed after mutation detection in the VCAN gene.
  
  
  RESULTS
  The first index patient of this French family was referred to us because of a chronic uveitis since infancy; this uveitis was associated with exudative retinal detachment in the context of a severe uncharacterized familial vitreoretinopathy. Genetic linkage was obtained to the VCAN locus, and we further identified a new pathogenic mutation at the highly conserved splice acceptor site in intron 7 of the VCAN gene (c.4004-2A>T), which produced aberrantly spliced VCAN transcripts.
  
  
  CONCLUSIONS
  Extensive molecular investigation allowed us to classify this familial vitreoretinopathy as Wagner syndrome. This study illustrates the need to confirm clinical diagnosis by molecular genetic testing and adds new ocular phenotypes to the Wagner syndrome, such as vascular and inflammatory features.
authors: Université Paris-Descartes, Centre Cochin Ambulatoire d’Ophtalmologie, Assistance Publique Hôpitaux de Paris, France.
authors: Antoine P
authors: AP
authors: Brézin
authors: Brigitte
authors: B
authors: Nedelec
authors: Amandine
authors: A
authors: Barjol
authors: Pierre-Raphael
authors: PR
authors: Rothschild
authors: Marc
authors: M
authors: Delpech
authors: Sophie
authors: S
authors: Valleix
mesh_terms: D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D005602:France; D056726:Genetic Association Studies; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007438:Introns; D008297:Male; D009154:Mutation; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D022821:RNA Splice Sites; D012326:RNA Splicing; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D012163:Retinal Detachment / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053675:Versicans / Q000235:genetics* / Q000378:metabolism / Q000172:deficiency; D018630:Vitreoretinopathy, Proliferative / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D014822:Vitreous Body / Q000378:metabolism* / Q000473:pathology
chemical_list: D022821:RNA Splice Sites; C508322:VCAN protein, human; D053675:Versicans