Phenotypic expression of a PRPF8 gene mutation in a Large African American family

To describe the phenotype and determine the genetic cause of autosomal dominant retinitis pigmentosa (adRP) in a large African American family.

Fourteen members from 4 generations were evaluated clinically. Visual field measurements were made for most, and electroretinography, Tübinger perimetry, and optical coherence tomographic testing were done for individual family members. Genetic screening was performed on a recently introduced adRP microarray that contains approximately 400 mutations from 13 genes.

All of the affected members had a type 1 form of adRP, characterized by early onset of symptoms for visual impairment, marked central and peripheral vision loss, nondetectable electroretinographic responses, and decreased macular thickness on optical coherence tomographic testing. Two variants in the PRPF8 gene were identified in the proband, H2309R and IVS41-4G-->A. The H2309R mutation segregated with the disease in the family, whereas the IVS41-4G-->A variant did not.

The severe form of adRP was caused by the PRPF8 H2309R variant, whereas the IVS41-4G-->A variant was benign.

PRPF8 mutations should be suspected in patients with a type 1 form of adRP. A combination of advanced clinical workup and comprehensive genetic testing is essential for the precise diagnosis of diseases with high genetic heterogeneity such as RP.