Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41431-017-0082-2
Title: A clinical and molecular characterisation of CRB1-associated maculopathy
Authors: Khan, K.N
Robson, A
Mahroo, O.A.R
Arno, G
Inglehearn, C.F
Armengol, M
Waseem, N
Holder, G.E 
Carss, K.J
Raymond, L.F
Webster, A.R
Moore, A.T
McKibbin, M
Van Genderen, M.M
Poulter, J.A
Michaelides, M
Keywords: crumbs homologue 1 protein
protein
unclassified drug
CRB1 protein, human
eye protein
membrane protein
nerve protein
adult
allele
Article
clinical article
electronic patient record
female
follow up
genetic association
genetic screening
genotype phenotype correlation
heterozygote
human
infant
macular degeneration
male
next generation sequencing
ophthalmoscopy
optical coherence tomography
peripheral retina
phenotype
priority journal
retina maculopathy
retrospective study
visual acuity
young adult
adolescent
child
electronic health record
genetic association study
genetic predisposition
genetics
newborn
pathology
pathophysiology
photoreceptor outer segment
preschool child
Adolescent
Adult
Alleles
Child
Child, Preschool
Electronic Health Records
Eye Proteins
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genetic Testing
Humans
Infant
Infant, Newborn
Macular Degeneration
Male
Membrane Proteins
Nerve Tissue Proteins
Retinal Photoreceptor Cell Outer Segment
Young Adult
Issue Date: 2018
Publisher: Nature Publishing Group
Citation: Khan, K.N, Robson, A, Mahroo, O.A.R, Arno, G, Inglehearn, C.F, Armengol, M, Waseem, N, Holder, G.E, Carss, K.J, Raymond, L.F, Webster, A.R, Moore, A.T, McKibbin, M, Van Genderen, M.M, Poulter, J.A, Michaelides, M (2018). A clinical and molecular characterisation of CRB1-associated maculopathy. European Journal of Human Genetics 26 (5) : 687-694. ScholarBank@NUS Repository. https://doi.org/10.1038/s41431-017-0082-2
Rights: Attribution 4.0 International
Abstract: To 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. © 2018 The Authors.
Source Title: European Journal of Human Genetics
URI: https://scholarbank.nus.edu.sg/handle/10635/179042
ISSN: 10184813
DOI: 10.1038/s41431-017-0082-2
Rights: Attribution 4.0 International
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