Figures & data
Figure 1. OPTOS image of a male RPGR patient showing the typical peripheral ‘bone spicule’ like pigmentary changes and signs of foveal atrophy. The inner retinal vessels are also attenuated due to the loss of outer retinal cells (photoreceptors) through physiological autoregulation of blood supply – this is not believed to be pathogenic.
Figure 2. X-linked female carrier AF image showing the tapetal-like reflex centred on the fovea and patchy peripheral pigmentation. The mosaic picture is due to random X-inactivation generating clones of normal or degenerate photoreceptors. Since as with males, the degeneration takes time to manifest, a clearer X-linked carrier phenotype will generally be seen on the mothers of affected men rather than their daughters.
Figure 3. Schematic representation of the RPGR gene structure and the main alternatively spliced transcripts. Note that there is normally a splice donor site within the 5ʹ region of ORF15. In gene therapy, the cDNA encoding the gene is transcribed as a primary RNA transcript in the nucleus and may be subject to splicing. Hence disabling this splice donor site is also an essential part of codon optimisation.
Figure 4. Major RPGR protein isoforms (constitutive RPGREXON1-19 and RPGRORF15) schematic representation. RLD: RCC1-like domain, BD: basic domain.
