Copyright © 2007 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 81, Issue 1, 147-157, 1 July 2007
doi:10.1086/518426
Report
Recurrent Mutation in the First Zinc Finger of the Orphan Nuclear Receptor NR2E3 Causes Autosomal Dominant Retinitis Pigmentosa
Frauke Coppieters*, a, Bart P. Leroy*, a, b, Diane Beysena, Jan Hellemansa, Karolien De Bosscherc, Guy Haegemanc, Kirsten Robberechtb, Wim Wuytsd, Paul J. Couckea and Elfride De Baerea, 
, 
a From the Center for Medical Genetics, Ghent University, Ghent, Belgium
b Department of Ophthalmology, Ghent University, Ghent, Belgium
c Laboratory for Eukaryotic Gene Expression and Signal Transduction (LEGEST) Department of Molecular Biology, Ghent University, Ghent, Belgium
d Center for Medical Genetics, Antwerp
Address for correspondence and reprints: Dr. Elfride De Baere, Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium* These two authors contributed equally to this work.
Abstract
“Autosomal dominant retinitis pigmentosa” (adRP) refers to a genetically heterogeneous group of retinal dystrophies, in which 54% of all cases can be attributed to 17 disease loci. Here, we describe the localization and identification of the photoreceptor cell-specific nuclear receptor gene NR2E3 as a novel disease locus and gene for adRP. A heterozygous mutation c.166G→A (p.Gly56Arg) was identified in the first zinc finger of NR2E3 in a large Belgian family affected with adRP. Overall, this missense mutation was found in 3 families affected with adRP among 87 unrelated families with potentially dominant retinal dystrophies (3.4%), of which 47 were affected with RP (6.4%). Interestingly, affected members of these families display a novel recognizable NR2E3-related clinical subtype of adRP. Other mutations of NR2E3 have previously been shown to cause autosomal recessive enhanced S-cone syndrome, a specific retinal phenotype. We propose a different pathogenetic mechanism for these distinct dominant and recessive phenotypes, which may be attributed to the dual key role of NR2E3 in the regulation of photoreceptor-specific genes during rod development and maintenance.
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