Novel Insights into RPGR Exon ORF15: Could G-Quadruplex Folding Lead to Challenging Sequencing?

Hereditary retinal dystrophies (HRDs) represent a wide group of chronic and hereditary disorders affecting the retina, which constitute an important source of disability. Among inherited retinal dystrophies, retinitis pigmentosa (RP) represents the most genetically and clinically heterogeneous group. X-linked forms (OMIM 26800), the most severe subtypes of this disease, account for about 15% of RP cases. RPGR, one of the most X-linked RP involved genes, involved in ciliogenesis, microtubule organization and regulation of transport in primary cilia, presents a splicing variant, called exon ORF15, which represents a mutational hot spot in a huge number of patients. The most challenge peculiarity of exon ORF15 is its repetitive nature, especially of guanine (G)-rich sequences, that makes it very difficult to screen. Thus, we investigate the possible molecular causes that determine such difficulties by an in-silico approach, evaluating the possibility that, due to its nature, exon ORF15 could show a G-quadruplex structure. All the three algorithms exploited confirmed the possibility that several G-quadruplex could be folded in RPGR exon ORF15, providing new insights towards a better sequencing approach to RPGR diagnostic screening.