Late-Onset Autosomal Dominant Macular Degeneration Caused by Deletion of the CRX Gene.
In: Ophthalmology, Jg. 130 (2023), Heft 1, S. 68-76
academicJournal
Zugriff:
Purpose: To characterize the phenotype observed in a case series with macular disease and determine the cause.
Design: Multicenter case series.
Participants: Six families (7 patients) with sporadic or multiplex macular disease with onset at 20 to 78 years, and 1 patient with age-related macular degeneration.
Methods: Patients underwent ophthalmic examination; exome, genome, or targeted sequencing; and/or polymerase chain reaction (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 8 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 hybridization. Microsatellite genotypes showed that these 7 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.
(Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
Titel: |
Late-Onset Autosomal Dominant Macular Degeneration Caused by Deletion of the CRX Gene.
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Autor/in / Beteiligte Person: | Yahya, S ; Smith, CEL ; Poulter, JA ; McKibbin, M ; Arno, G ; Ellingford, J ; Kämpjärvi, K ; Khan, MI ; Cremers, FPM ; Hardcastle, AJ ; Castle, B ; Steel, DHW ; Webster, AR ; Black, GC ; El-Asrag, ME ; Ali, M ; Toomes, C ; Inglehearn, CF |
Zeitschrift: | Ophthalmology, Jg. 130 (2023), Heft 1, S. 68-76 |
Veröffentlichung: | 2000- : New York : Elsevier ; <i>Original Publication</i>: Rochester, Minn., American Academy of Ophthalmology., 2023 |
Medientyp: | academicJournal |
ISSN: | 1549-4713 (electronic) |
DOI: | 10.1016/j.ophtha.2022.07.023 |
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