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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 |
Appears in Collections: | Elements Staff Publications |
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