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Late-Onset Autosomal Dominant Macular Degeneration Caused by Deletion of the CRX Gene

Authors :
Samar Yahya
Claire E.L. Smith
James A. Poulter
Martin McKibbin
Gavin Arno
Jamie Ellingford
Kati Kämpjärvi
Muhammad I. Khan
Frans P.M. Cremers
Alison J. Hardcastle
Bruce Castle
David H.W. Steel
Andrew R. Webster
Graeme C. Black
Mohammed E. El-Asrag
Manir Ali
Carmel Toomes
Chris F. Inglehearn
Stuart Ingram
Rachel Taylor
Forbes Manson
Panagiotis Sergouniotis
Nikolas Pontikos
Michael Cheetham
Alessia Fiorentino
Susan Downes
Jing Yu
Stephanie Halford
Suzanne Broadgate
Veronica van Heyningen
John C. Ambrose
Prabhu Arumugam
Roel Bevers
Marta Bleda
Freya Boardman-Pretty
Christopher R. Boustred
Helen Brittain
Mark J. Caulfield
Georgia C. Chan
Greg Elgar
Tom Fowler
Adam Giess
Angela Hamblin
Shirley Henderson
Tim J.P. Hubbard
Rob Jackson
Louise J. Jones
Dalia Kasperaviciute
Melis Kayikci
Athanasios Kousathanas
Lea Lahnstein
Sarah E.A. Leigh
Ivonne U.S. Leong
Javier F. Lopez
Fiona Maleady-Crowe
Meriel McEntagart
Federico Minneci
Loukas Moutsianas
Michael Mueller
Nirupa Murugaesu
Anna C. Need
Peter O’Donovan
Chris A. Odhams
Christine Patch
Mariana Buongermino Pereira
Daniel Perez-Gil
John Pullinger
Tahrima Rahim
Augusto Rendon
Tim Rogers
Kevin Savage
Kushmita Sawant
Richard H. Scott
Afshan Siddiq
Alexander Sieghart
Samuel C. Smith
Alona Sosinsky
Alexander Stuckey
Mélanie Tanguy
Ana Lisa Taylor Tavares
Ellen R.A. Thomas
Simon R. Thompson
Arianna Tucci
Matthew J. Welland
Eleanor Williams
Katarzyna Witkowska
Suzanne M. Wood
Source :
Ophthalmology, 130, 68-76, Ophthalmology, 130, 1, pp. 68-76
Publication Year :
2023
Publisher :
Elsevier BV, 2023.

Abstract

To characterize the phenotype observed in a case series with macular disease and determine the cause.Multicenter case series.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.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.Clinical phenotypes, genomic findings, and a hypothesis explaining the mechanism underlying disease in these patients.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.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.

Details

ISSN :
01616420
Volume :
130
Database :
OpenAIRE
Journal :
Ophthalmology
Accession number :
edsair.doi.dedup.....507827933b913ead226b13ff8c186891