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Atta Ur Rehman, Quy Ai Ngo, Inmaculada Martin-Merida, Blanca Garcia-Sandoval, Carmen Ayuso, Carlo Rivolta; A rare chromosomal rearrangement in the X-linked opsin gene array is associated with retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5407.
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To characterize the genetic basis of putative progressive blue cone monochromacy in a Spanish patient with poor central vision and achromatopsia
A 48-year-old male patient underwent a thorough ophthalmic examination, including ERG and Farnsworth-Munsell tests. Following DNA extraction from his peripheral blood leukocytes, the genes for the red [OPN1LW (L)] and green cone opsins [OPN1MW (M)], as well as their locus control region (LCR), were investigated by PCR amplification and Sanger sequencing.
The patient presented with a history of progressive loss of visual acuity, which was 20/100 in both eyes at the time of examination, and difficulties in distinguishing colors. Fundus examination revealed normal maculae, optic disks, and vessels. No pigmentary deposits were present. Visual field indicated an absolute scotoma in the upper temporal quadrant and relative scotomas in the center. ERG showed abolished cone response but normal rod activity; the Farnsworth-Munsell test revealed an alteration in the protan axis. Sequence analysis of the X-linked opsin gene array revealed no alteration in the LCR, but a chromosomal rearrangement resulting in the fusion of the L and M genes at the level of exon 3. More specifically, exons 1 and 2 of the L gene remained intact while exons 4, 5, 6 were deleted. Conversely, the M gene retained complete exons 4, 5, and 6, and lost exons 1 and 2. A hybrid exon 3 was created by the in-frame fusion of the 5’ part of exon 3 from the L gene (L3) and the 3’ part of exon 3 from the M gene (M3), resulting in the recombinant sequence 5’-L1-L2-L3/M3-M4-M5-M6-3’. The composite exon 3 harbored the ‘LVAVA’ haplotype, previously shown to result in blue cone monochromacy or cone-rod degeneration by altering the correct pre-mRNA splicing of these cone opsin genes.
We report a rare genetic rearrangement resulting in a hybrid cone opsin gene and a LVAVA haplotype, possibly underlying degenerative blue cone monochromacy
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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