RPE65 retinitis pigmentosa
Several different genes have been implicated in RP. Mutations have been identified in a number of genes that encode retina-specific proteins, including RPE65, AIPL1, CRB1, CRX, GUCY2D, and RPGRIP1.
RPE65 retinitis pigmentosa is one of the most severe form of inherited retinal dystrophy.
RPE65-linked retinitis affects from between 2,750-3,300 people in North America + EU 5 main countries (Hartong et al. Lancet 2006; 368: 1795–809). This dystrophy accounts for 5% of all retinal dystrophies and 20% of blinding diseases in school age children (Source: Orphanet).
In infants, RPE65 retinitis pigmentosa is characterised by severe night blindness and moderate photophobia.
The RPE65 protein, located in the RPE, is key component of in the visual cycle. RPE65 converts all-trans retinal back to 11-cis-retinal, enabling regeneration of the visual pigment. Mutations in RPE65 lead to a disruption of the visual cycle, resulting in reduced photoreceptor function and visual loss from early life.
Clinical presentation of RPE65 patients
Diagnosis is established early, since affected children exhibit visual impairment within the first year of life. Visual function may subsequently improve, but deteriorates by adolescence, leading to blindness.
Affected patients display severely impaired night vision from birth, and nystagmus is usually evident from the first weeks of life. Once children begin to walk, they display a preference for areas with good lighting and have poor visual acuity. Funduscopy reveals moderate attenuation of retinal vessels, and in adulthood the appearance of pigment deposits and macular atrophy. Photopic and scotopic ERG responses are absent from a young age. The absence of retinal autofluorescence is a specific indicator of RPE65 mutation.
Appearance of the fundus
Funduscopy image from a 22-year-old patient with retinitis pigmentosa caused by a RPE65 mutation. Photo courtesy of Christian Hamel.