Autosomal Dominant Retinitis Pigmentosa Mapped on Chromosome 19q (adRP19q): Phenotype, Electrophysiology Tests and Genetic Counselling

Abstract

Abstract: : Purpose: To investigate the clinical variation of the phenotype in patients with a mutation in the PRPF31 gene mapped on chromosome 19q. Methods: Twenty members of a family with adRP19q took part in the study. Nine subjects were normal and donated a blood sample as a comparison group. Eleven with the mutation were evaluated with, fundus exam, electrophysiology tests and a questionnaire about the age of onset of RP symptoms and general health. They all donated a blood sample for genetic investigations. Results: Symptomatic patients were classified into two groups based on the history of the disease: type I with early onset of symptoms, higher rate of progression with central visual loss within the I-II decade of life. The type II had later onset of symptoms, slower progression and good central vision still preserved in the IV decade of life. All symptomatic symptomatic patients had severe generalised retinal dysfunction of rod and cone systems on the electrophysiology tests, restriction of the visual field and classic features of RP on fundus exam. Six members were asymptomatic with normal fundus exam. The electrophysiology tests showed a poorly formed or undetectable S cone ERG in all asymptomatic individuals, the maximal ERG was mildly subnormal in 50% of them and the rod ERG as well as the PERG was subnormal bilaterally in 30% of them. No systemic associations were found in any examined member. Conclusions: adRP19q shows bimodal expressivity. An inverse relationship of severity between parents and offspring was observed: severely affected parents had more mildly affected children than mildly affected parents. Based on these observations it has been postulated that an allelic effect modulates the severity of disease: the normal allele inherited from the non-carrier parent seems to be determinant for the phenotype. Further studies on molecular genetics are needed to confirm the hypothesis.

Keywords: retinal degenerations: hereditary • gene/expression • electrophysiology: clinical