Dataset Information

A 73,128 bp de novo deletion encompassing the OPN1LW/OPN1MW gene cluster in sporadic Blue Cone Monochromacy: a case report.

ABSTRACT: BACKGROUND:Blue Cone Monochromacy (BCM) is a rare congenital cone dysfunction disorder with X-linked recessive mode of inheritance. BCM is caused by mutations at the OPN1LW/MW cone opsin gene cluster including deletions of the locus control region (LCR) and/or parts of the gene cluster. We aimed at investigating the clinical presentation, genetic cause and inheritance underlying a sporadic case of BCM. CASE PRESENTATION:We report a 24-year-old male presenting with congenital photophobia, nystagmus and colour vision abnormalities. There was no history of retinal dystrophy in the family. Clinical diagnosis of BCM was supported by genetic investigations of the patient and his family members. Molecular genetic analysis of the OPN1LW/OPN1MW gene cluster revealed a novel deletion of about 73 kb in the patient encompassing the LCR. The deletion was absent in the X-chromosomes of both the mother and transmitting grandfather. CONCLUSIONS:The present report provides the clinical findings and the genetic basis underlying a sporadic BCM case which is caused by a de novo deletion within the OPN1LW/MW gene cluster originating from the mother's germline due to Alu-repeat mediated recombination. This is the first report of a de novo deletion resulting in BCM, highlighting the importance to consider BCM and perform genetic testing for this condition in male patients with cone dysfunction also in the absence of a positive family history.

SUBMITTER: Buena-Atienza E

PROVIDER: S-EPMC6019650 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A 73,128 bp de novo deletion encompassing the OPN1LW/OPN1MW gene cluster in sporadic Blue Cone Monochromacy: a case report.

Buena-Atienza Elena E Nasser Fadi F Kohl Susanne S Wissinger Bernd B

BMC medical genetics 20180626 1

<h4>Background</h4>Blue Cone Monochromacy (BCM) is a rare congenital cone dysfunction disorder with X-linked recessive mode of inheritance. BCM is caused by mutations at the OPN1LW/MW cone opsin gene cluster including deletions of the locus control region (LCR) and/or parts of the gene cluster. We aimed at investigating the clinical presentation, genetic cause and inheritance underlying a sporadic case of BCM.<h4>Case presentation</h4>We report a 24-year-old male presenting with congenital photo ...[more]

PMID: 29940872

Similar Datasets

Project description:BackgroundBlue Cone Monochromacy (BCM) is an X-linked retinopathy caused by mutations in the OPN1LW / OPN1MW gene cluster, encoding long (L)- and middle (M)-wavelength sensitive cone opsins. Recent evidence shows sufficient structural integrity of cone photoreceptors in BCM to warrant consideration of a gene therapy approach to the disease. In the present study, the vision in BCM is examined, specifically seeking clinically-feasible outcomes for a future clinical trial.MethodsBCM patients (n = 25, ages 5-72) were studied with kinetic and static chromatic perimetry, full-field sensitivity testing, and eye movement recordings. Vision at the fovea and parafovea was probed with chromatic microperimetry.ResultsKinetic fields with a Goldmann size V target were generally full. Short-wavelength (S-) sensitive cone function was normal or near normal in most patients. Light-adapted perimetry results on conventional background lights were abnormally reduced; 600-nm stimuli were seen by rods whereas white stimuli were seen by both rods and S-cones. Under dark-adapted conditions, 500-nm stimuli were seen by rods in both BCM and normals. Spectral sensitivity functions in the superior retina showed retained rod and S-cone functions in BCM under dark-adapted and light-adapted conditions. In the fovea, normal subjects showed L/M-cone mediation using a 650-nm stimulus under dark-adapted conditions, whereas BCM patients had reduced sensitivity driven by rod vision. Full-field red stimuli on bright blue backgrounds were seen by L/M-cones in normal subjects whereas BCM patients had abnormally reduced and rod-mediated sensitivities. Fixation location could vary from fovea to parafovea. Chromatic microperimetry demonstrated a large loss of sensitivity to red stimuli presented on a cyan adapting background at the anatomical fovea and surrounding parafovea.ConclusionsBCM rods continue to signal vision under conditions normally associated with daylight vision. Localized and retina-wide outcome measures were examined to evaluate possible improvement of L/M-cone-based vision in a clinical trial.

Project description:Novel therapeutic approaches for treating inherited retinal degenerations (IRDs) prompt a need to understand which patients with impaired vision have the anatomical potential to gain from participation in a clinical trial. We used supervised machine learning to predict foveal function from foveal structure in blue cone monochromacy (BCM), an X-linked congenital cone photoreceptor dysfunction secondary to mutations in the OPN1LW/OPN1MW gene cluster. BCM patients with either disease-associated large deletion or missense mutations were studied and results compared with those from subjects with other forms of IRD and various degrees of preserved central structure and function. A machine learning technique was used to associate foveal sensitivities and best-corrected visual acuities to foveal structure in IRD patients. Two random forest (RF) models trained on IRD data were applied to predict foveal function in BCM. A curve fitting method was also used and results compared with those of the RF models. The BCM and IRD patients had a comparable range of foveal structure. IRD patients had peak sensitivity at the fovea. Machine learning could successfully predict foveal sensitivity (FS) results from segmented or un-segmented optical coherence tomography (OCT) input. Application of machine learning predictions to BCM at the fovea showed differences between predicted and measured sensitivities, thereby defining treatment potential. The curve fitting method provided similar results. Given a measure of visual acuity (VA) and foveal outer nuclear layer thickness, the question of how many lines of acuity would represent the best efficacious result for each BCM patient could be answered. We propose that foveal vision improvement potential in BCM is predictable from retinal structure using machine learning and curve fitting approaches. This should allow estimates of maximal efficacy in patients being considered for clinical trials and also guide decisions about dosing.

Dataset Information

A 73,128 bp de novo deletion encompassing the OPN1LW/OPN1MW gene cluster in sporadic Blue Cone Monochromacy: a case report.

Publications

A 73,128 bp de novo deletion encompassing the OPN1LW/OPN1MW gene cluster in sporadic Blue Cone Monochromacy: a case report.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets