Blue cone monochromatism: clinical findings in patients with mutations in the red/green opsin gene cluster

Kellner, Ulrich; Wissinger, Bernd; Tippmann, Sabine; Kohl, Susanne; Kraus, H; Foerster, Michael

doi:10.1007/s00417-004-0921-z

Cited by 34 publications

(30 citation statements)

References 20 publications

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“…Evidence of progressive central retinal cone loss was present in some patients and macular atrophy in later stages, thereby confirming previous observations (e.g., Ayyagari et al, 1999;Nathans et al, 1989;Kellner et al, 2004). This disease pattern does show some resemblance to that in the rhodopsin knockout mouse, but it is less cataclysmic.…”

Section: Consequences Of Congenital Cone Opsin Deficiency On Conessupporting

confidence: 77%

Human Cone Visual Pigment Deletions Spare Sufficient Photoreceptors to Warrant Gene Therapy

et al. 2013

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Human X-linked blue-cone monochromacy (BCM), a disabling congenital visual disorder of cone photoreceptors, is a candidate disease for gene augmentation therapy. BCM is caused by either mutations in the red (OPN1LW) and green (OPN1MW) cone photoreceptor opsin gene array or large deletions encompassing portions of the gene array and upstream regulatory sequences that would predict a lack of red or green opsin expression. The fate of opsin-deficient cone cells is unknown. We know that rod opsin null mutant mice show rapid postnatal death of rod photoreceptors. Using in vivo histology with high-resolution retinal imaging, we studied a cohort of 20 BCM patients (age range 5-58) with large deletions in the red/green opsin gene array. Already in the first years of life, retinal structure was not normal: there was partial loss of photoreceptors across the central retina. Remaining cone cells had detectable outer segments that were abnormally shortened. Adaptive optics imaging confirmed the existence of inner segments at a spatial density greater than that expected for the residual blue cones. The evidence indicates that human cones in patients with deletions in the red/green opsin gene array can survive in reduced numbers with limited outer segment material, suggesting potential value of gene therapy for BCM.

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Section: Consequences Of Congenital Cone Opsin Deficiency On Conessupporting

confidence: 77%

Human Cone Visual Pigment Deletions Spare Sufficient Photoreceptors to Warrant Gene Therapy

et al. 2013

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“…This is in stark contrast to rods, where expression of mutant rhodopsin not only compromises the viability of the rod photoreceptor but also neighboring cones. However, there are cases where males with BCM show progressive, widespread retinal degeneration (Ayyagari et al, 1999a, Ayyagari, Kakuk, Toda, Coats, Bingham, Szczesny, Felius & Sieving, 1999b, Kellner, Wissinger, Tippmann, Kohl, Kraus & Foerster, 2004, Michaelides, Johnson, Simunovic, Bradshaw, Holder, Mollon, Moore & Hunt, 2005, Nathans et al, 1989), so our understanding of this condition is incomplete.…”

Section: Discussionmentioning

confidence: 99%

Deletion of the X-linked opsin gene array locus control region (LCR) results in disruption of the cone mosaic

et al. 2010

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Blue-cone monochromacy (BCM) is an X-linked condition in which long- (L−) and middle- (M−) wavelength-sensitive cone function is absent. Due to the X-linked nature of the condition, female carriers are spared from a full manifestation of the associated defects but can show visual symptoms, including abnormal cone electroretinograms. Here we imaged the cone mosaic in four females carrying an L/M array with deletion of the locus control region, resulting in an absence of L/M opsin gene expression (effectively acting as a cone opsin knockout). On average, they had cone mosaics with reduced density and disrupted organization compared to normal trichromats. This suggests that the absence of opsin in a subset of cones results in their early degeneration, with X-inactivation the likely mechanism underlying phenotypic variability in BCM carriers.

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“…It has been speculated that the rearrangement of the X-chromosome pigment gene array may not only cause dichromacy but also a cone dystrophy [3,15,16]. Support for this hypothesis came from in vitro studies showing that specific mutations within the X-chromosome pigment gene array can cause disruption of folding, half-life and light activation of the cone opsin molecule and, thus, may cause progressive retinal dystrophies [12].…”

Section: Discussionmentioning

confidence: 98%

“…[27,39,45] More severe forms of colour vision deficiency involve the degeneration, dysfunction or absence of at least two types of cone photoreceptors, as observed in patients with incomplete or complete achromatopsia [2,3,[15][16][17]47] or severe cone dystrophies [36].…”

Section: Introductionmentioning

confidence: 99%

Progressive cone dystrophy with deutan genotype and phenotype

Scholl

Kremers

Besch

et al. 2005

Graefe's Arch Clin Exp Ophthalmo

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This patient exhibits a coincidence of progressive cone dystrophy and deuteranopia. The molecular genetic data of the L/M-pigment gene array is consistent with the deutan phenotype. It cannot be excluded that the rearrangement of the X-chromosome pigment gene array is responsible for the cone dystrophy in this patient. It is, however, suggested that the dichromacy and the cone dystrophy have different and independent genetic origins.

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Blue cone monochromatism: clinical findings in patients with mutations in the red/green opsin gene cluster

Cited by 34 publications

References 20 publications

Human Cone Visual Pigment Deletions Spare Sufficient Photoreceptors to Warrant Gene Therapy

Human Cone Visual Pigment Deletions Spare Sufficient Photoreceptors to Warrant Gene Therapy

Deletion of the X-linked opsin gene array locus control region (LCR) results in disruption of the cone mosaic

Progressive cone dystrophy with deutan genotype and phenotype

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