EXTENDED REPORT

Further evidence of genetic heterogeneity in familial exudative vitreoretinopathy; exclusion of EVR1, EVR3, and EVR4 in a large autosomal dominant pedigree

C Toomes¹, L M Downey¹, H M Bottomley¹, H A Mintz-Hittner² and C F Inglehearn¹

¹ Molecular Medicine Unit, School of Medicine, University of Leeds, UK
² Department of Ophthalmology and Visual Science, University of Texas-Houston Medical School, TX, USA

Correspondence to:
Correspondence to:
Dr Carmel Toomes
Molecular Medicine Unit, Clinical Sciences Building, St James’s University Hospital, Leeds LS9 7TF, UK; c.toomes{at}leeds.ac.uk

Background/aims: Familial exudative vitreoretinopathy (FEVR) is an inherited blinding condition characterised by abnormal development of the retinal vasculature. The aim of this study was to perform linkage analysis in a large family affected with FEVR to determine whether the mutation involved was in one of the three known autosomal dominant FEVR loci or in another as yet unidentified gene.

Methods: Genomic DNA samples from family members were polymerase chain reaction (PCR) amplified with fluorescently tagged microsatellite markers spanning the EVR1/EVR4 locus (11q13-14) and the EVR3 locus (11p12-13). The resulting PCR products were resolved using an automated DNA sequencer and the alleles sized. These data were used to construct haplotypes across each locus and linkage analysis was performed to prove or exclude linkage.

Results: The clinical evaluation in this family suggested features typical of FEVR, with deficient peripheral retinal vascularisation being the common phenotype in all affected individuals. However, linkage analysis proved that this family has a form of FEVR genetically distinct from the EVR1, EVR3 and EVR4 loci.

Conclusion: The exclusion of linkage in this family to any of the known FEVR loci proves the existence of a fourth locus for autosomal dominant FEVR and shows that this rare disorder is far more heterogeneous than previously thought.

Abbreviations: FEVR, familial exudative vitreoretinopathy

Keywords: familial exudative vitreoretinopathy; heterogeneity

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Downey, L M, Bottomley, H M, Sheridan, E, Ahmed, M, Gilmour, D F, Inglehearn, C F, Reddy, A, Agrawal, A, Bradbury, J, Toomes, C (2006). Reduced bone mineral density and hyaloid vasculature remnants in a consanguineous recessive FEVR family with a mutation in LRP5.. Br. J. Ophthalmol. 90: 1163-1167 [Abstract] [Full Text]  
• Masckauchan, T. N. H., Kitajewski, J. (2006). Wnt/Frizzled Signaling in the Vasculature: New Angiogenic Factors in Sight. Physiology 21: 181-188 [Abstract] [Full Text]  
• Toomes, C, Downey, L M, Bottomley, H M, Mintz-Hittner, H A, Inglehearn, C F (2005). Further evidence of genetic heterogeneity in familial exudative vitreoretinopathy; exclusion of EVR1, EVR3, and EVR4 in a large autosomal dominant pedigree. J. Med. Genet. 42: 291-291 [Full Text]