The PROM1 mutation p.R373C causes an autosomal dominant bull's eye maculopathy associated with rod, rod-cone, and macular dystrophy.

Michaelides, Michel; Gaillard, Marie-Claire; Escher, Pascal; Tiab, Leila; Bedell, Matthew; Borruat, François-Xavier; Barthelmes, Daniel; Carmona, Ruben; Zhang, Kang; White, Edward; McClements, Michelle; Robson, Anthony G; Holder, Graham E; Bradshaw, Keith; Hunt, David M; Webster, Andrew R; Moore, Anthony T; Schorderet, Daniel F; Munier, Francis L (2010). The PROM1 mutation p.R373C causes an autosomal dominant bull's eye maculopathy associated with rod, rod-cone, and macular dystrophy. Investigative ophthalmology & visual science, 51(9), pp. 4771-4780. Association for Research in Vision and Ophthalmology 10.1167/iovs.09-4561

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PURPOSE To characterize in detail the phenotype of five unrelated families with autosomal dominant bull's eye maculopathy (BEM) due to the R373C mutation in the PROM1 gene. METHODS Forty-one individuals of five families of Caribbean (family A), British (families B, D, E), and Italian (family C) origin, segregating the R373C mutation in PROM1, were ascertained. Electrophysiological assessment, fundus autofluorescence (FAF) imaging, fundus fluorescein angiography (FFA), and optical coherence tomography (OCT) were performed in available subjects. Mutation screening of PROM1 was performed. RESULTS The R373C mutant was present heterozygously in all affected patients. The age at onset was variable and ranged between 9 and 58 years, with most of the individuals presenting with reading difficulties. Subjects commonly had a mild to moderate reduction in visual acuity except for members of family C who experienced markedly reduced central vision. The retinal phenotype was characterized by macular dystrophy, with retinal pigment epithelial mottling in younger subjects, progressing to typical BEM over time, with the development of macular atrophy in older patients. In addition, all members of family C had typical features of RP. The electrophysiological findings were variable both within and between families. CONCLUSIONS Mutations in PROM1 have been described to cause a severe form of autosomal recessive RP in two families of Indian and Pakistani descent. The results of this study have demonstrated that a distinct redundant PROM1 mutation (R373C) can also produce an autosomal dominant, fully penetrant retinopathy, characterized by BEM with little inter- and intrafamilial variability, and retinal dystrophy with variable rod or rod-cone dysfunction and marked intra- and interfamilial variability, ranging from isolated maculopathy without generalized photoreceptor dysfunction to maculopathy associated with very severe rod-cone dysfunction.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology

UniBE Contributor:

Escher, Pascal

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0146-0404

Publisher:

Association for Research in Vision and Ophthalmology

Language:

English

Submitter:

PD Dr. Pascal Escher

Date Deposited:

10 Jul 2017 13:55

Last Modified:

31 Jul 2017 08:31

Publisher DOI:

10.1167/iovs.09-4561

PubMed ID:

20393116

BORIS DOI:

10.7892/boris.101775

URI:

https://boris.unibe.ch/id/eprint/101775

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