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dc.contributor.authorKhan, Kamron N
dc.contributor.authorRobson, Anthony
dc.contributor.authorMahroo, Omar AR
dc.contributor.authorArno, Gavin
dc.contributor.authorInglehearn, Chris F
dc.contributor.authorArmengol, Monica
dc.contributor.authorWaseem, Naushin
dc.contributor.authorHolder, Graham E
dc.contributor.authorCarss, Keren
dc.contributor.authorRaymond, Lucy
dc.contributor.authorWebster, Andrew R
dc.contributor.authorMoore, Anthony T
dc.contributor.authorMcKibbin, Martin
dc.contributor.authorvan Genderen, Maria M
dc.contributor.authorPoulter, James A
dc.contributor.authorMichaelides, Michel
dc.contributor.authorUK Inherited Retinal Disease Consortium
dc.date.accessioned2018-11-23T00:32:23Z
dc.date.available2018-11-23T00:32:23Z
dc.date.issued2018-05
dc.identifier.issn1018-4813
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285816
dc.description.abstractTo date, over 150 disease-associated variants in CRB1 have been described, resulting in a range of retinal disease phenotypes including Leber congenital amaurosis and retinitis pigmentosa. Despite this, no genotype-phenotype correlations are currently recognised. We performed a retrospective review of electronic patient records to identify patients with macular dystrophy due to bi-allelic variants in CRB1. In total, seven unrelated individuals were identified. The median age at presentation was 21 years, with a median acuity of 0.55 decimalised Snellen units (IQR = 0.43). The follow-up period ranged from 0 to 19 years (median = 2.0 years), with a median final decimalised Snellen acuity of 0.65 (IQR = 0.70). Fundoscopy revealed only a subtly altered foveal reflex, which evolved into a bull's-eye pattern of outer retinal atrophy. Optical coherence tomography identified structural changes-intraretinal cysts in the early stages of disease, and later outer retinal atrophy. Genetic testing revealed that one rare allele (c.498_506del, p.(Ile167_Gly169del)) was present in all patients, with one patient being homozygous for the variant and six being heterozygous. In trans with this, one variant recurred twice (p.(Cys896Ter)), while the four remaining alleles were each observed once (p.(Pro1381Thr), p.(Ser478ProfsTer24), p.(Cys195Phe) and p.(Arg764Cys)). These findings show that the rare CRB1 variant, c.498_506del, is strongly associated with localised retinal dysfunction. The clinical findings are much milder than those observed with bi-allelic, loss-of-function variants in CRB1, suggesting this in-frame deletion acts as a hypomorphic allele. This is the most prevalent disease-causing CRB1 variant identified in the non-Asian population to date.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectUK Inherited Retinal Disease Consortium
dc.subjectHumans
dc.subjectMacular Degeneration
dc.subjectGenetic Predisposition to Disease
dc.subjectEye Proteins
dc.subjectMembrane Proteins
dc.subjectNerve Tissue Proteins
dc.subjectAlleles
dc.subjectAdolescent
dc.subjectAdult
dc.subjectChild
dc.subjectChild, Preschool
dc.subjectInfant
dc.subjectInfant, Newborn
dc.subjectFemale
dc.subjectMale
dc.subjectRetinal Photoreceptor Cell Outer Segment
dc.subjectYoung Adult
dc.subjectGenetic Testing
dc.subjectGenetic Association Studies
dc.subjectElectronic Health Records
dc.titleA clinical and molecular characterisation of CRB1-associated maculopathy.
dc.typeArticle
prism.endingPage694
prism.issueIdentifier5
prism.publicationDate2018
prism.publicationNameEur J Hum Genet
prism.startingPage687
prism.volume26
dc.identifier.doi10.17863/CAM.33160
dcterms.dateAccepted2017-12-05
rioxxterms.versionofrecord10.1038/s41431-017-0082-2
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-05
dc.contributor.orcidRaymond, Lucy [0000-0003-2652-3355]
dc.contributor.orcidPoulter, James A [0000-0003-2048-5693]
dc.identifier.eissn1476-5438
rioxxterms.typeJournal Article/Review
cam.issuedOnline2018-02-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International