Journal article
Disease expression of RP1 mutations causing autosomal dominant retinitis pigmentosa
Investigative ophthalmology & visual science, Vol.41(7), pp.1898-1908
06/2000
PMID: 10845615
Abstract
To determine the disease expression in heterozygotes for mutations in the RP1 gene, a newly identified cause of autosomal dominant retinitis pigmentosa (adRP). Screening strategies were used to detect disease-causing mutations in the RP1 gene, and detailed studies of phenotype were performed in a subset of the detected RP1 heterozygotes using electroretinography (ERG), psychophysics, and optical coherence tomography (OCT). Seventeen adRP families had heterozygous RP1 changes. Thirteen families had the Arg677ter mutation, whereas four others had one of the following: Pro658 (1-bp del), Ser747 (1-bp del), Leu762-763 (5-bp del), and Tyr1053 (1-bp del). In Arg677ter RP1 heterozygotes, there was regional retinal variation in disease, with the far peripheral inferonasal retina being most vulnerable; central and superior temporal retinal regions were better preserved. The earliest manifestation of disease was rod dysfunction, detectable as reduced rod ERG photoresponse maximum amplitude, even in heterozygotes with otherwise normal clinical, functional, and OCT cross-sectional retinal imaging results. At disease stages when cone abnormalities were present, there was greater rod than cone dysfunction. Patients with the RP1 frameshift mutations showed similarities in phenotype to those with the Arg677ter mutation. Earliest disease expression of RP1 gene mutations causing adRP involves primarily rod photoreceptors, and there is a gradient of vulnerability of retinopathy with more pronounced effects in the inferonasal peripheral retina. At other disease stages, cone function is also affected, and severe retina-wide degeneration can occur. The nonpenetrance or minimal disease expression in some Arg677ter mutation-positive heterozygotes suggests important roles for modifier genes or environmental factors in RP1-related disease.
Details
- Title: Subtitle
- Disease expression of RP1 mutations causing autosomal dominant retinitis pigmentosa
- Creators
- Samuel G Jacobson - Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, USA. jacobsos@mail.med.upenn.eduArtur V CideciyanAlessandro IannacconeRichard G WeleberGerald A FishmanAlbert M MaguireLouisa M AffatigatoJean BennettEric A PierceMichael DancigerDebora B FarberEdwin M Stone
- Resource Type
- Journal article
- Publication Details
- Investigative ophthalmology & visual science, Vol.41(7), pp.1898-1908
- PMID
- 10845615
- NLM abbreviation
- Invest Ophthalmol Vis Sci
- ISSN
- 0146-0404
- eISSN
- 1552-5783
- Publisher
- United States
- Grant note
- EY-08426 / NEI NIH HHS EY-05627 / NEI NIH HHS EY-10539 / NEI NIH HHS
- Language
- English
- Date published
- 06/2000
- Academic Unit
- The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
- Record Identifier
- 9983980001402771
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