Molecular genetic analysis in the hereditary vitreoretinopathies

Abstract

‘Hereditary vitreoretinopathy’ encompasses a group of inherited disorders characterized by an abnormal appearance to the vitreous gel of the eye. These conditions have a reputation among ophthalmologists for consisting of rare syndromes which often have diverse and overlapping pathology. They can be very phenotypically variable. The consistent clinical feature is the abnormal vitreous, which is a structure in the eye about which much remains unknown. In the last few years there has been an explosion in the number of causative mutations identified in the hereditary vitreoretinopathies and, in some disorders, genetic analysis now offers molecular characterisation and a way of clarifying these conditions for clinicians.

The aim of the research project was to use clinical examination of the vitreous gel of the eye to target molecular genetic analysis in the laboratory in order to clarify the clinical diagnosis of an inherited vitreoretinopathy. Individuals and families were identified with a clinical diagnosis of a hereditary vitreoretinopathy. Molecular genetic techniques were employed to analyse these autosomal dominant conditions. A splice site mutation of the CSPG2 gene was identified in Wagner syndrome. Three novel mutations were found in type 2 Stickler syndrome and a protocol was developed for future analysis of the COL11A1 gene from a genomic DNA source. In a family with clinical features of Stickler syndrome an area of linkage was identified which may contain a new candidate gene for Stickler syndrome.

Several of the hereditary vitreoretinopathies are associated with a high rate of retinal detachment. Syndromic causes of retinal detachment are rare but investigation of the hereditary vitreoretinopathies may lead to a greater understanding of the mechanisms underlying the more common non-syndromic retinal detachment, which is a cause of significant ocular morbidity.