Phenotypes and genotypes in families with hereditary tapetoretinal degenerations

Abstract: The purpose of the study was to characterise the phenotype with emphasis on electroretinography in four different types of hereditary retinal degeneration and to correlate it to a genotype when possible. Two methods were used: full-field electroretinography for objective assessment of retinal function and mutation screening of blood samples for detection of gene alterations. Electroretinograms from patients with central areolar choroidal dystrophy demonstrated a reduction of the cone b-wave amplitude and a prolongation of the implicit time indicating a generalised cone disease which is slowly progressive. Patients with choroderemia and a deletion of the CHM gene presented two different phenotypes, one mild and one severe, even though the genotype was identical in all examined patients, indicating that the severity of the phenotype is not solely a function of the CHM gene. Three families with autosomal dominant retinitis pigmentosa and different mutations in the rhodopsin and the peripherin gene were studied. The rhodopsin mutation Arg-135-Try is associated with a severe phenotype while patients with the mutation Pro-267-Leu have a mild retinal degeneration with a nearly normal electroretinogram early in the natural course of the disease. The peripherin mutation Phe-211-Leu is associated with a phenotype including early loss of rod function and a macular degeneration. Three families with X-linked retinitis pigmentosa and mutations in the RPGR gene had severely reduced electroretinograms and in one of the families also the carriers were visually disabled. A family with progressive autosomal dominant cone-rod dystrophy had an intrafamiliar variability of the phenotype with different degrees of rod involvement. It is concluded that both full-field electroretinography and DNA analysis should be included in the investigation of patients with hereditary retinal degenerations in order to achieve a reliable diagnosis and prognosis.