May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Elucidation of the Molecular Causes of Wagner Disease
Author Affiliations & Notes
  • K. Nikopoulos
    Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Department of Human Genetics,
  • A. Mukhopadhyay
    Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Department of Human Genetics,
  • A. Maugeri
    Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Department of Human Genetics,
  • C. E. van Nouhuys
    Canisius-Wilhelmina Ziekenhuis, Nijmegen, The Netherlands
  • C. J. F. Boon
    Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Department of Ophthalmology,
  • J. M. M. Hooymans
    Department of Ophthalmology, University of Groningen, Groningen, The Netherlands
  • D. Wittebol-Post
    Department of Ophthalmology, University Medical Centre Utrecht, Utrecht, The Netherlands
  • P. R. van den Biessen
    Department of Ophthalmology, University Medical Centre Utrecht, Utrecht, The Netherlands
  • C. B. Hoyng
    Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Department of Ophthalmology,
  • F. P. M. Cremers
    Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Department of Human Genetics,
  • Footnotes
    Commercial Relationships K. Nikopoulos, None; A. Mukhopadhyay, None; A. Maugeri, None; C.E. van Nouhuys, None; C.J.F. Boon, None; J.M.M. Hooymans, None; D. Wittebol-Post, None; P.R. van den Biessen, None; C.B. Hoyng, None; F.P.M. Cremers, None.
  • Footnotes
    Support EU RTN ‘RETNET’ MRTN-CT-2003-504003, the Algemene Nederlandse Vereniging ter Voorkoming van Blindheid, F.P. Fischer Stichting, Gelderse Blindenverenig,Stichting Blindenhulp, Stichting voor Ooglijders
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1319. doi:
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    • Get Citation

      K. Nikopoulos, A. Mukhopadhyay, A. Maugeri, C. E. van Nouhuys, C. J. F. Boon, J. M. M. Hooymans, D. Wittebol-Post, P. R. van den Biessen, C. B. Hoyng, F. P. M. Cremers; Elucidation of the Molecular Causes of Wagner Disease. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1319.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: Recently, mutations of the splice sites flanking exon 8 in CSPG2/Versican were found in patients with Wagner disease and erosive vitreoretinopathy. The purpose of this study was to determine the genetic defect in six families with Wagner disease in which no splice site mutations of CSPG2/Versican were identified.

Methods:: Haplotype analysis using microsatellite markers around CSPG2/Versican and COL2A1 was performed. Sequence analysis was performed for exons 2-15 of CSPG2/Versican and exon 2 of COL2A1. Transcripts from different isoforms of CSPG2/Versican were quantified by QRT-PCR using total RNA from fresh blood.

Results:: Unlike the families with exon 8 splice site mutations, QPCR did not reveal the characteristic upregulation of the V2 and V3 splice variants for any of the families, with the exception of a Chinese family showing a significant increase of V2 (>400-fold) and V3 (>30-fold). We found cosegregation of the 5q14.3/CSPG2 region in four families and the 12q13.11/COL2A1 region in one family. In the latter family a stop mutation (p.C64X) was identified in exon 2 of COL2A1. Patients from this family show the typical features of Wagner disease i.e. an optically empty vitreous, formation of preretinal membrane, lattice degeneration and rhegmatogenous retinal detachments. No extra-ocular Stickler syndrome features, such as orofacial or skeletal abnormities were found. Mutation analysis of CSPG2/Versican and exon 2 of COL2A1 for the other families is ongoing.

Conclusions:: The identification of a stop mutation in exon 2 of COL2A1 in a clinically typical Wagner disease family lead us to propose that patients with Wagner disease can carry mutations in CSPG2/Versican or COL2A1

Keywords: mutations • gene screening • proteoglycans/glycosaminoglycans 
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