Novel non-sense mutation in RP2 (c.843-844insT/p.Arg282fs) is associated with a severe phenotype of retinitis pigmentosa without evidence of primary retinal pigment epithelium involvement

© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ. Retinitis pigmentosa (RP) relates to a heterogeneous group of rod-cone dystrophies of varying genetic aetiology. There is currently great interest in gene replacement therapy. Phenotyping is of particular importance because some RP genes are expressed ubiquitously and it is critically important to understand which retinal layer is primarily affected. RP2 is increasingly diagnosed in patients suffering from X-linked RP, which causes outer retinal degeneration. We present a case of a previously unreported null mutation in RP2 associated with severe RP. Loss of the retinal pigment epithelium (RPE) was noted in the central macula but not around the disc or peripherally. There was therefore no evidence of independent degeneration of the RPE. Hence despite expression in all retinal cells, RP2 deficiency does not appear to be pathogenic to the RPE. This observation may be helpful in considering the promoter and route of delivery of adeno-associated viral gene therapy vectors encoding RP2.