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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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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.
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.
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.
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
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