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

Détails

Ressource 1Télécharger: BIB_8CA3332522F1.P001.pdf (2422.24 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_8CA3332522F1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The PROM1 mutation p.R373C causes an autosomal dominant bull's eye maculopathy associated with rod, rod-cone, and macular dystrophy.
Périodique
Investigative Ophthalmology and Visual Science
Auteur(s)
Michaelides M., Gaillard M.C., Escher P., Tiab L., Bedell M., Borruat F.X., Barthelmes D., Carmona R., Zhang K., White E., McClements M., Robson A.G., Holder G.E., Bradshaw K., Hunt D.M., Webster A.R., Moore A.T., Schorderet D.F., Munier F.L.
ISSN
1552-5783[electronic], 0146-0404[linking]
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
51
Numéro
9
Pages
4771-4780
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Résumé
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.
Mots-clé
Adolescent, Adult, Age of Onset, Antigens, CD/genetics, Family Health, Female, Fovea Centralis/pathology, Genes, Dominant, Glycoproteins/genetics, Humans, Male, Middle Aged, Pedigree, Peptides/genetics, Phenotype, Point Mutation, Retinal Cone Photoreceptor Cells/pathology, Retinal Rod Photoreceptor Cells/pathology, Retinitis Pigmentosa/ethnology, Retinitis Pigmentosa/genetics, Tomography, Optical Coherence, Young Adult
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/10/2010 14:53
Dernière modification de la notice
20/08/2019 14:50
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