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Invest Ophthalmol Vis Sci. 2019 Mar 1;60(4):1192-1203. doi: 10.1167/iovs.18-26084.

Macular Dystrophy and Cone-Rod Dystrophy Caused by Mutations in the RP1 Gene: Extending the RP1 Disease Spectrum.

Author information

1
Department of Ophthalmology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
2
Department of Human Genetics, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
3
Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.
4
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
5
Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
6
Department of Ophthalmology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
7
The Netherlands Institute for Neuroscience (NIN-KNAW), Amsterdam, The Netherlands.
8
Department of Computational Biology, Unit of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
9
Service of Medical Genetics, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
10
Department of Genetics and Genome Biology, University of Leicester, Leicester, United Kingdom.
11
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
12
Yuko Wada Eye Clinic, Sendai, Japan.
13
Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
14
Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
15
Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Abstract

Purpose:

To describe the clinical and genetic spectrum of RP1-associated retinal dystrophies.

Methods:

In this multicenter case series, we included 22 patients with RP1-associated retinal dystrophies from 19 families from The Netherlands and Japan. Data on clinical characteristics, visual acuity, visual field, ERG, and retinal imaging were extracted from medical records over a mean follow-up of 8.1 years.

Results:

Eleven patients were diagnosed with autosomal recessive macular dystrophy (arMD) or autosomal recessive cone-rod dystrophy (arCRD), five with autosomal recessive retinitis pigmentosa (arRP), and six with autosomal dominant RP (adRP). The mean age of onset was 40.3 years (range 14-56) in the patients with arMD/arCRD, 26.2 years (range 18-40) in adRP, and 8.8 years (range 5-12) in arRP patients. All patients with arMD/arCRD carried either the hypomorphic p.Arg1933* variant positioned close to the C-terminus (8 of 11 patients) or a missense variant in exon 2 (3 of 11 patients), compound heterozygous with a likely deleterious frameshift or nonsense mutation, or the p.Gln1916* variant. In contrast, all mutations identified in adRP and arRP patients were frameshift and/or nonsense variants located far from the C-terminus.

Conclusions:

Mutations in the RP1 gene are associated with a broad spectrum of progressive retinal dystrophies. In addition to adRP and arRP, our study provides further evidence that arCRD and arMD are RP1-associated phenotypes as well. The macular involvement in patients with the hypomorphic RP1 variant suggests that macular function may remain compromised if expression levels of RP1 do not reach adequate levels after gene augmentation therapy.

PMID:
30913292
DOI:
10.1167/iovs.18-26084

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