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Disease expression of RP1 mutations causing autosomal dominant retinitis pigmentosa.
Invest Ophthalmol Vis Sci. 2000 Jun; 41(7):1898-908.IO

Abstract

PURPOSE

To determine the disease expression in heterozygotes for mutations in the RP1 gene, a newly identified cause of autosomal dominant retinitis pigmentosa (adRP).

METHODS

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).

RESULTS

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.

CONCLUSIONS

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.

Authors+Show Affiliations

Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, USA. jacobsos@mail.med.upenn.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10845615

Citation

Jacobson, S G., et al. "Disease Expression of RP1 Mutations Causing Autosomal Dominant Retinitis Pigmentosa." Investigative Ophthalmology & Visual Science, vol. 41, no. 7, 2000, pp. 1898-908.
Jacobson SG, Cideciyan AV, Iannaccone A, et al. Disease expression of RP1 mutations causing autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2000;41(7):1898-908.
Jacobson, S. G., Cideciyan, A. V., Iannaccone, A., Weleber, R. G., Fishman, G. A., Maguire, A. M., Affatigato, L. M., Bennett, J., Pierce, E. A., Danciger, M., Farber, D. B., & Stone, E. M. (2000). Disease expression of RP1 mutations causing autosomal dominant retinitis pigmentosa. Investigative Ophthalmology & Visual Science, 41(7), 1898-908.
Jacobson SG, et al. Disease Expression of RP1 Mutations Causing Autosomal Dominant Retinitis Pigmentosa. Invest Ophthalmol Vis Sci. 2000;41(7):1898-908. PubMed PMID: 10845615.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Disease expression of RP1 mutations causing autosomal dominant retinitis pigmentosa. AU - Jacobson,S G, AU - Cideciyan,A V, AU - Iannaccone,A, AU - Weleber,R G, AU - Fishman,G A, AU - Maguire,A M, AU - Affatigato,L M, AU - Bennett,J, AU - Pierce,E A, AU - Danciger,M, AU - Farber,D B, AU - Stone,E M, PY - 2000/6/14/pubmed PY - 2000/6/17/medline PY - 2000/6/14/entrez SP - 1898 EP - 908 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 41 IS - 7 N2 - PURPOSE: To determine the disease expression in heterozygotes for mutations in the RP1 gene, a newly identified cause of autosomal dominant retinitis pigmentosa (adRP). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/10845615/Disease_expression_of_RP1_mutations_causing_autosomal_dominant_retinitis_pigmentosa_ L2 - https://iovs.arvojournals.org/article.aspx?volume=41&issue=7&page=1898 DB - PRIME DP - Unbound Medicine ER -