Gene Therapy for X-Linked Retinitis Pigmentosa

Abstract

Copyright: © 2013 Shu X. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Retinitis Pigmentosa (RP) is a group of heterogeneous genetic disorders with a worldwide prevalence of 1 in 4000 individuals [1]. RP can be inherited in autosomal, X-linked or mitochondrial format. X-linked RP (XLRP) is one of the most severe forms of retinopathies, accounting for about 10-20% of all RP cases. Mutations in the Retinitis Pigmentosa Gtpase Regulator (RPGR) gene are the major cause of XLRP, accounting for 70 to 80% of affected XLRP cases [2]. The initially identified RPGR (RPGRex1-19) contains 19 exons and encodes for a predicted 90 KDa protein [3]. A subsequent study identified a large C-terminal exon, called ORF15, in the major functional form (RPGRORF15). The exon ORF15 encodes a repetitive glycine and glutamic acid-rich domain with a evolutionary conserved basic C-terminal domain, and harbors a high frequency of reading-frameshift and premature stop mutations, producing truncated proteins of varying length [4]. More than 300 RPGR mutations have been reported, most causing XLRP, a few causing human cone-rod, cone, or macular dystrophies, or syndromal forms of XLRP with primary ciliary dyskinesia and hearing loss [5].