Unexpected Retinal Expression In A Three-generation Family Of Females Who Turned Out To Be Carriers Of X-linked Retinitis Pigmentosa

Abstract

Purpose: : Three women (daughter, mother and maternal grand mother) were seen for a genetic consultation due to familial recurrence of diffuse loss of RPE revealing the underlying choroïdal vessels seen as broad "tiger-stripe" striations. Ophthalmologic follow-up and genetic analysis were performed to solve this particular phenotype.

Methods: : A 46 year-old woman (II2) was seen for a progressive decrease in visual acuity (80/200RLE) which could not be corrected. Upon ophthalmological examination her fundus displayed diffuse "tiger-stripe" striations (LRE). Her sister and two brothers as well as her 5 nephews and 4 nieces had no known visual deficiency. Conversely, her 68 year-old mother (I1) presented since infancy with unilateral amblyopia and her fundus presented the same "tiger-stripe" striations (LRE). Finally, while her 24 year-old son had no visual problem, her 21 year-old daughter (III2) presented a moderate and well corrected myopia but her fundus was similar to that of her mother and grand-mother. The ORF15 exon of the RPGR gene was screened for mutation using direct sequencing.

Results: : II2 presented with bilateral keratoconus, diffuse loss of RPE at the fundus but normal visual field and ERG recordings. I1 had unilateral high myopia (-9Do) accounting for amblyopia, unrecordable ERG, a large central scotoma (LE) and enlarged blindspot (RE) at the visual field, marked (LE) and slight (RE) macular atrophy at the fundus in addition to the "tiger-stripe" striations. III2 had normal visual acuity and visual field, diffuse loss of RPE only but severely altered ERGs. Owing to the incomplete penetrance and the presence of unilateral myopia in P1, we suspected an X-linked transmission accounted for by RPGR mutation which screening evidenced a 4 bp deletion in the ORF15 leading to the apparition of a premature stop codon.

Conclusions: : The existence of unusual retinal manifestations in women with no related affected males does not rule out X-linked transmission especially when highly asymmetric or even unilateral myopia and variable expressivity or incomplete penetrance are noted. In the family described here, III2 had thus a 50% risk of having a son carrying a severe form of RP.

Keywords: retinal degenerations: hereditary • clinical (human) or epidemiologic studies: natural history