The PROM1 mutation p.R373C causes an autosomal dominant bull's eye maculopathy associated with rod, rod-cone, and macular dystrophy.
OBJECTIVE
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.
Michaelides
Michel
M
UCL Institute of Ophthalmology, London, United Kingdom. michel.michaelides@ucl.ac.uk
Gaillard
Marie-Claire
MC
Escher
Pascal
P
Tiab
Leila
L
Bedell
Matthew
M
Borruat
François-Xavier
FX
Barthelmes
Daniel
D
Carmona
Ruben
R
Zhang
Kang
K
White
Edward
E
McClements
Michelle
M
Robson
Anthony G
AG
Holder
Graham E
GE
Bradshaw
Keith
K
Hunt
David M
DM
Webster
Andrew R
AR
Moore
Anthony T
AT
Schorderet
Daniel F
DF
Munier
Francis L
FL
D000071916:AC133 Antigen; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015703:Antigens, CD / Q000235:genetics*; D005192:Family Health; D005260:Female; D005584:Fovea Centralis / Q000473:pathology; D005799:Genes, Dominant; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010455:Peptides / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology*; D012174:Retinitis Pigmentosa / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D041623:Tomography, Optical Coherence; D055815:Young Adult
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides
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