Phenotype-genotype correlations in autosomal dominant retinitis pigmentosa caused by RHO, D190N

Abstract

Purpose: To phenotype a family with RHO (Asp190Asn or D190N) dominantly inherited retinitis pigmentosa (RP) and to describe an approach to surveying affected families.

Methods: Four patients from a family with a history of autosomal dominant RP had complete clinical examinations and underwent full-field electroretinography (ERG), fundus autofluorescence (AF) imaging, and genetic testing. One patient had microperimetry (MP) mapping.

Results: The patients' ages ranged from 6 years to 47 years. The proband, the father, had fundoscopic findings typical of RP. A small hyperfluorescent ring centered at the fovea was apparent on AF. MP showed preservation of central 7 degrees of visual field within this ring. The three children were all asymptomatic with visual acuity of 20/15 in each eye. One child had mild retinal pigment epithelium migration on fundoscopy; the other two children had normal fundoscopic examinations. Two children showed increased parafoveal AF. In the two affected children, average ERG b-wave implicit times were delayed in scotopic conditions, and maximal ERG tracings had abnormal waveforms. Genetic analysis confirmed that two of three asymptomatic children carried the D190N allele.

Conclusions: Patients with RHO (D190N) autosomal dominant retinitis pigmentosa (adRP) can show classic signs of RP on fundus examination and may be able to maintain good central visual acuity into adulthood. By combining clinical examination with AF imaging and electrophysiology, it is possible to offer presymptomatic clinical evaluation to families with this RP.

Figure 1. Color fundus photographs

A. 47 year old man with D190N adRP, right eye. Optic nerve has mild pallor and there is extensive intraretinal pigment migration in the mid-periphery. Note the incidental choroidal nevus 3.9 × 3.36 mm along the inferotemporal arcade. B. 11 year old son affected with adRP, left eye. Note the mild RPE migration inferonasally. C. 9 year old son without RP, left eye. Optic nerve without pallor and macula with good foveal reflex. D. 7 year old son affected with adRP, right eye. Optic nerve without pallor and macula with good foveal reflex, clinically indistinguishable from panel C.

Figure 2. Autofluorescence imaging

A. 47 year old man with D190N adRP, right eye. Macula with small hyperfluorescent ring. B. 11 year old son affected with adRP, left eye. Macula with large hyperfluorescent ring (black arrows.) C. 9 year old son without RP, left eye. Macular autofluorescence normal. D. 7 year old son affected with adRP, right eye. Macula with early, large hyperfluorescent ring (black arrows) similar to panel B.

Figure 3

Microperimetry 10-2 mapping of right eye in case 1. Red shows scotoma and green (seven degrees of field) is retina which is well functioning.

Figure 4

ERG tracings of cases 2, 3, and 4 under rod specific, maximum scotopic, photopic 30Hz flicker and transient photopic conditions. (a) right eye (b) left eye. Scales and normal range indicated below the tracings.

Figure 4

ERG tracings of cases 2, 3, and 4 under rod specific, maximum scotopic, photopic 30Hz flicker and transient photopic conditions. (a) right eye (b) left eye. Scales and normal range indicated below the tracings.

Figure 5

Three generation pedigree of the family with known RHO, D190N affected individuals. Note autosomal dominant inheritance is supported by the presence of consecutive affected generations and male-to-male transmission.