RPGR mutation analysis and disease: an update

Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene are the most common single cause of retinitis pigmentosa, accounting for up to 15 to 20% of cases in Caucasians. A total of 240 different RPGR mutations have been reported, including 24 novel ones in this work, which are associated with X-linked retinitis pigmentosa (XLRP) (95%), cone, cone-rod dystrophy, or atrophic macular atrophy (3%), and syndromal retinal dystrophies with ciliary dyskinesia and hearing loss (2%). All disease-causing mutations occur in one or more RPGR isoforms containing the carboxyl-terminal exon open reading frame 15 (ORF15), which are widely expressed but show their highest expression in the connecting cilia of rod and cone photoreceptors. Of reported RPGR mutations, 55% occur in a glutamic acid-rich domain within exon ORF15, which accounts for only 31% of the protein. RPGR forms complexes with a variety of other proteins and appears to have a role in microtubular organization and transport between photoreceptor inner and outer segments.