BIMODAL EXPRESSIVITY IN DOMINANT RETINITIS-PIGMENTOSA GENETICALLY LINKED TO CHROMOSOME 19Q

A clinical, psychophysical, and electrophysiologic study was undertake n of two autosomal dominant retinitis pigmentosa pedigrees with a gene tic mutation assigned to chromosome 19q by Linkage analysis. Members w ith the abnormal haplotype were either symptomatic with adolescent ons et nyctalopia, restricted visual fields, and non-detectable electroret inographic responses by 30 years of age, or asymptomatic with normal f undus appearance and minimal or no psychophysical or electroretinograp hic abnormalities. There was no correlation in the severity in parents and their offspring. Pedigree analysis suggested that although the of fspring of parents with the genetic mutation were at 50% risk of havin g the genetic defect, the risk of being symptomatic during a working l ifetime was only 31%. Such bimodal phenotypic expressivity in these pa rticular pedigrees may be explained by a second, allelic genetic influ ence and may be a phenomenon unique to this genetic locus. Genetic cou nselling in families expressing this phenotype can only be based on ha plotype analysis since clinical investigations, even in the most elder ly, would not preclude the presence of the mutant gene.