RP2 Mutations Cause Variable Phenotypes in Carrier Females in Two Families With Retinitis Pigmentosa

Abstract

Purpose: : Although pathogenic mutations in RPGR cause widely varied clinical symptoms in female carriers, RP2 mutations are infrequently reported to cause a pronounced carrier phenotype. Herein we assess symptoms among hemizygote males and heterozygote females in 2 families with retinitis pigmentosa (RP) due to mutations in RP2.

Methods: : Pedigrees were compiled from family history interviews. The inheritance pattern for one family was X-linked and the other initially appeared autosomal dominant; both families have a history of females with advanced symptoms of RP. Individuals from 2 generations of RFS119 (2 female, 2 male) and 3 generations of RFS021 (3 female, 2 male) were available for genetic testing and a full clinical exam including ISCEV standard electroretinography (ERG).

Results: : Family

Conclusions: : Both RP2 mutations result in early onset severe RP in hemizygous males and a widely variable spectrum of disease severity in heterozygous carriers. The severity of symptoms observed among carriers can mimic a dominant pattern of inheritance thereby confounding genetic testing and accurate genetic counseling. Mutations in RP2 as well as RPGR should be considered potential culprits for moderate-to-severe disease manifestation among carrier females.

Keywords: retinal degenerations: hereditary • mutations • electrophysiology: clinical