A Second French Wagner Family Case Revealed By A Severe Uveitis Associated With A New Vcan Splice Mutation

Abstract

Purpose: : Wagner syndrome (OMIM_143200) is a dominantly inherited vitreoretinopathy, typically characterized by an optically empty vitreous and progressive chorioretinal degeneration. Other ocular features have variably been reported, but it remains difficult to determine whether they are part of the disease. We recently reported a French Wagner family with uveitis (Brézin et al., Mol Vis. 2011), and we describe here an additional Wagner kindred with severe postoperative chronic uveitis. The affected members are heterozygous for a new VCAN splice mutation.

Methods: : Detailed phenotypic characterization and VCAN mutation screening were performed on 9 available family members through three generations. Quantitative RT-PCR of versican isoforms is ongoing.

Results: : A 44 year-old female presented with postoperative severe chronic bilateral uveitis after uneventful cataract surgery. On examination, at nine months postoperatively visual acuity was 20/32 OD and 20/200 OS, slit-lamp examination showed decentered IOLs in keeping with capsular fibrosis and posterior synechiaes in both eyes. Laser flare meter values were elevated in both eyes: 16±1 OD, 119,5±1,5 OS (in photons/ms ; normal value<10). IOP values were within normal limits. Fundus examination revealed an optically empty vitreous with equatorial circumferential avascular preretinal membrane, foveal ectopia with temporally dragged retinal vessels and some degree of chorioretinal atrophy. SD-OCT demonstrated a peculiar dense posterior hyaloid forming a bridge over the foveal pit. A systematic familial examination unraveled a compatible clinical and OCT phenotype in the proband‘s mother and one of her sisters. We identified a novel heterozygous T to A substitution at the sixth base of the VCAN splice acceptor site of intron 7 (c.4004-6 T>A) segregating with the disease state.

Conclusions: : Although inflammatory manifestations have not been initially described in Wagner syndrome, a total of three Wagner families with uveitis have now been recognized. Considering that the αGAG and βGAG domains of versican are involved in the binding of a series of cytokines, Wagner syndrome may be a disease with inflammatory susceptibility. Wagner disease should be added to the list of causes of uveitis or to that of masquerade syndromes presenting as uveitis.

Keywords: retinal degenerations: hereditary • genetics