title: A family with Wagner syndrome with uveitis and a new versican mutation.
abstract: OBJECTIVE
  To report the clinical and molecular findings of a kindred with Wagner syndrome (WS) revealed by intraocular inflammatory features.
  
  
  METHODS
  Eight available family members underwent complete ophthalmologic examination, including laser flare cell meter measurements. Collagen, type II, alpha 1, versican (VCAN), frizzled family receptor 4, low density lipoprotein receptor-related protein 5, tetraspanin 12, and Norrie disease (pseudoglioma) genes were screened with direct sequencing.
  
  
  RESULTS
  The index case was initially referred for unexplained severe and chronic postoperative bilateral uveitis following a standard cataract surgery procedure. Clinical examination of the proband revealed an optically empty vitreous with avascular vitreous strands and veils, features highly suggestive of WS. The systematic familial ophthalmologic examination identified three additional unsuspected affected family members who also presented with the WS phenotype, including uveitis for one of them. We identified a novel c.4004-6T>A nucleotide substitution at the acceptor splice site of intron 7 of the VCAN gene that segregated with the disease phenotype.
  
  
  CONCLUSIONS
  We present a family with WS with typical WS features and intraocular inflammatory manifestations associated with a novel splice site VCAN mutation. Beyond the structural role in the retinal-vitreous architecture, versican is also emerging as a pivotal mediator of the inflammatory response, supporting uveitis predisposition as a clinical manifestation of WS.
authors.affiliation: AP-HP, Groupe Hospitalier Cochin-Hôtel-Dieu, Service d'ophtalmologie, Université Paris Descartes, Sorbonne Paris Cité, Paris, France ; INSERM, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Pierre-Raphaël
authors.initials: PR
authors.lastname: Rothschild
authors.forename: Antoine P
authors.initials: AP
authors.lastname: Brézin
authors.forename: Brigitte
authors.initials: B
authors.lastname: Nedelec
authors.forename: Cyril
authors.initials: C
authors.lastname: Burin des Roziers
authors.forename: Tiffany
authors.initials: T
authors.lastname: Ghiotti
authors.forename: Lucie
authors.initials: L
authors.lastname: Orhant
authors.forename: Mathieu
authors.initials: M
authors.lastname: Boimard
authors.forename: Sophie
authors.initials: S
authors.lastname: Valleix
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D003198:Computer Simulation; D005190:Family; D005260:Female; D005654:Fundus Oculi; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012162:Retinal Degeneration / Q000150:complications* / Q000235:genetics*; D014605:Uveitis / Q000150:complications* / Q000235:genetics*; D053675:Versicans / Q000172:deficiency* / Q000235:genetics; D055815:Young Adult
chemical_list: D022821:RNA Splice Sites; D012333:RNA, Messenger; C508322:VCAN protein, human; D053675:Versicans