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Late-onset autosomal dominant macular degeneration caused by deletion of the CRX gene

Yahya, Samar; Smith, Claire El; Poulter, James A; McKibbin, Martin; Arno, Gavin; Ellingford, Jamie; Kämpjärvi, Kati; ... Inglehearn, Chris F; + view all (2022) Late-onset autosomal dominant macular degeneration caused by deletion of the CRX gene. Ophthalmology 10.1016/j.ophtha.2022.07.023. (In press). Green open access

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Abstract

PURPOSE: To characterise the phenotype observed in a case series with macular disease and determine the cause. DESIGN: Multi-centre case series. PARTICIPANTS: Six families (seven patients) with sporadic or multiplex macular disease with onset at 36-78 years, and one patient with age-related macular degeneration. METHODS: Patients underwent ophthalmic examination, exome, genome or targeted sequencing, and/or PCR amplification of the breakpoint followed by cloning and Sanger sequencing or direct Sanger sequencing. MAIN OUTCOME MEASURES: Clinical phenotypes, genomic findings and a hypothesis explaining the mechanism underlying disease in these patients. RESULTS: All eight cases carried the same deletion encompassing the genes TPRX1, CRX and SULT2A1, which was absent from 382 control individuals screened by breakpoint PCR and 13,096 Clinical Genetics patients with a range of other inherited conditions screened by array comparative genomic hybridisation. Microsatellite genotypes showed that these seven families are not closely related, but genotypes immediately adjacent to the deletion breakpoints suggest they may share a distant common ancestor. CONCLUSIONS: Previous studies had found that carriers for a single defective CRX allele that was predicted to produce no functional CRX protein had a normal ocular phenotype. Here we show that CRX whole-gene deletion in fact does cause a dominant late-onset macular disease.

Type: Article
Title: Late-onset autosomal dominant macular degeneration caused by deletion of the CRX gene
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ophtha.2022.07.023
Publisher version: https://doi.org/10.1016/j.ophtha.2022.07.023
Language: English
Additional information: © 2022 by the American Academy of Ophthalmology This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: CRX, SULT2A1, TPRX1, macular disease, retinal disease
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10153580
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