molecular research

As far as we know molecular research is being done in Zürich, Nijmegen and Tokushima.

In Zürich (Switzerland) they are in the process of trying to explain the pathology of the splice mutation. They are testing hypotheses of either haplo-insufficiency or disturbed isoform ratios by analyzing the expression of various VCAN transcript and protein isoforms. In the healthy vitreous, glycosaminoglycan-rich versican isoforms prevent clumping of collagen fibrils. Splicing defects in Wagner disease lead to drastic over expression of variant V2 carrying reduced attachment site for glycosamino glycans. This situation may lead to early liquefaction of the vitreous. See the images in the left column.

They are also analyzing a -Dutch- Wagner vitreous biopt. They want to make a quantitative statement about the expression of versican at the protein level by trying to isolate proteins from the virteous biopt. They are able to identify some of the naturally occurring variants of versican, due to variant specific antibodies that the Zimmermann group in Zurich has isolated. If protein levels mimick transcript levels, they expect variant 2- based on the transcript analysis published by Frans Cremers- to be overexpressed.

And finally they are in the process of finding a mouse model for Wagner disease.

On their website they offer genetic testing.

In Nijmegen (the Netherlands) researchers are looking for intronic mutations in the Dutch family  from Chinese origin from the article from Arijit Mukhopadhyay. They hope for an explanation in severity in symptoms between different family members and between members of different pedigrees with Wagner syndrome.

They too offer genetic testing.

In Tokushima (Japan) the researchers speculate that the c.4004-2A>G mutation in the CSPG2/versican gene may result in insufficient interactions between versican and various vitreous components, including HA (hyaluron acid) and type II collagen and thereby produce premature syneresis and degeneration in the vitreous gel. To test this hypothesis, functional experiments using mutant and wild-type versican cDNAs are under way in their laboratory.

phenotype - genotype

In Nijmegen they just started to more accurately phenotype Wagner syndrome to see if a connection can be made between the different mutations and difference in expression. They hope to find a predictive factor for severity in symptoms and adequate, evidence based, (prophylactic) treatment.


In Chicago Irene Maumenee is doing research on connective tissue disorders and glaucoma. She did research on the original Swiss pedigree in the 19-eighties.

In India Arijit Mukhopadhyay (from the article in mol. vis. 2006 on the Versican gene in the Dutch pedigree) is doing research on the role of the Versican gene in the trabecular meshwork and ciliary body.


in this section recent development are in focus. Please email us if you are aware of research in an aspect affecting Wagner syndrome, so (other) researchers know where others are working on. Please email us by clicking the icon.


page last modified Feb 14th 2010

Wagner syndrome

other Wagner variants?

Graeme Black (1999) described a vitreoretinopathy with a mutation in the Versican gene, on the 5-cM region of 5q13-14. He chooses not to label this as Wagner syndrome but as a hereditary developmental vitreoretinopathy. Until the precise gene defect has been established we will  agree with him. This kindred was earlier called family W2 in the article from Perveen at al. (1999).

All 13 affected patients had been diagnosed as such in the first decade of life; all 6 of these with a documented examination within the first 6 months of life showed signs of the disorder at that stage. The majority of affected individuals were severely visually handicapped. All affected adults had been registered blind, four with light perception only in one eye or no light perception in either eye.

Of the 13 affected individuals, 8 had a clear history of sudden reduction of vision secondary to retinal detachment in 1 or both eyes.

Besides these features the following are mentioned: 2 eyes (1p) with nystagmus, 2 with microphthalmia, 4 (3p) with posterior embryotoxon, 3 (2p) with iris hypoplasia, 1 with persistent hyperplastic primary vitreous.

A Novel Hereditary Developmental Vitreoretinopathy with Multiple Ocular Abnormalities Localizing to a 5-cM Region of Chromosome 5q13-q14

Graeme C. M. Black, FRCOphth, DPhil, Rahat Perveen, MSc, Wojtek Wiszniewski, BA, Christopher L. Dodd, FRCOphth, Dian Donnai, MRCP, David McLeod, FRCOphth

Ophthalmology. 1999 Nov;106(11):2074-81. 1999blackmanchesterW2.pdf

Extracellular matrix compo-nents in Wagner vitreous

Extracellular matrix compo-nents in normal vitreous

Predominantly Ocular-only Stickler Syndrome

A large family in Canada (Gupta et al, 2002) has been labelled as Wagner (type 2). However our point of view is chromosome based: we would like to reserve the name Wagner syndrome to the vitreoretinopathy on chromosome 5. Moreover we would like to use POSS for the disorder with no or little systemic features, with a mutation in exons 2, 30, 31 and possible others on the “Stickler” gene 12q13.11.

People with this mutation also have a different ocular phenotype: more retinal detachments (50%), no progressing cataract that needs removal in the 3rd or 4th decade, no chorioretinal athrophy and abnormal ERG. Also the vitreous phenotype is quite different from the Wagner vitreous.