Purchase this article with an account.
F. Schmid, E. Glaus, F. Cremers, B. Kloeckener-Gruissem, W. Berger, J. Neidhardt; Alterations in RPGR Splicing as a Potential Modifier of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4092.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Retinitis pigmentosa (RP) is characterized by the degeneration of predominantly rod photoreceptor cells. Approximately 70% of all X-linked RP cases carry mutations in the RPGR gene. In addition to RP, patients with RPGR mutations may show syndromic phenotypes affecting several other tissues. Splicing of RPGR produces different alternative transcript isoforms. In this study, we investigated whether splice defects occur in addition to mutations in RPGR, which may act as a modifier of the disease phenotype.
Patient-derived lymphoblastoid cell lines carrying RPGR mutations were screened for RPGR splice defects by RT-PCR. Furthermore, mutation-induced RPGR splice products were quantified by quantitative real-time RT-PCR. Additionally, alternatively spliced isoforms were also quantified in pools of different human donor tissues.
We identified several splice defects in RPGR of RP-patient derived cell lines. Some of these splice defects lead to changes in the expression level of novel transcript variants of RPGR. These novel transcripts showed either inclusion of a new exon designated 11a or skipping of exons 12, 14 or 15 of RPGR. Furthermore, they are differentially expressed among different human donor tissues from unaffected individuals and their expression might be regulated by nonsense-mediated mRNA decay. In total, we found that approximately 10% of RPGR isoforms are alternatively spliced in human retina.
Our results show that in addition to mutations in RPGR, splice defects affect a significant fraction of cases. These splice defects change the amount of alternative transcript isoforms of RPGR, whose expression is tissue-specifically regulated in unaffected individuals. Thus, changes in the expression pattern of an RPGR transcript variant may not only affect the retina, but could also interfere with RPGR function as a modifier of the phenotype.
This PDF is available to Subscribers Only