Retinitis pigmentosa caused by PDE6B mutations
PDE6B retinitis pigmentosa (RP) is an inherited retinal dystrophy that leads to blindness by midlife and is characterised by the progressive loss of photoreceptors, with or without the loss of retinal pigment epithelium cells.
One of the causative genes is PDE6B, which accounts for between 2 and 4% of RP cases, affecting between 3,600 and 5,400 people in North America + EU 5 main countries (Hartong et al. Lancet 2006; 368: 1795–809). The mutation og PDE6B gene is one of the most prevalent human mutation within autosomal recessive retinitis pigmentosa.
Rod PDE6 is an enzyme found in rod outer segments that plays a key role in the phototransduction cascade in rods (i.e., the process by which light is converted into electrical signals). It is a complex protein composed of two homologous catalytic subunits (PDE6α and PDE6ß) and two copies of an inhibitory subunit (PDE6γ). PDE6α and PDE6ß subunits are required for rod PDE6 activity.
Dysfunction of the PDE6 protein, and in particular its PDE6ß subunit, ultimately leads to cell death of rods, followed by cones, and consequent blindness.
Clinical presentation of PDE6ß retinitis pigmentosa
Affected children develop night blindness due to rod dysfunction. In adulthood, the peripheral visual field progressively decreases in daylight conditions, resulting in legal blindness upon reaching less than 20 degrees. Fundus examination reveals constriction of retinal vessels, pallor of the optic disc, pigment deposits in the peripheral retina, and a preserved macular zone. Patients generally show no detectable electroretinogram (ERG) response, although a daylight response may occasionally be detected. With time, the macula becomes atrophic, resulting in central blindness.