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M.-C. Gaillard, L. Tiab, T. Delarive, T. Favez, Cé. Agosti, B. Piguet, F. L. Munier, D. F. Schorderet; First Autosomal Dominant Prominin Related Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3737.
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© ARVO (1962-2015); The Authors (2016-present)
To describe the clinical feature and identify the gene causing an autosomal dominant retinitis pigmentosa (ADRP) associated with a bull eye’s maculoptathy in a large family.
16 individuals of a 5-generation Italian family affected with ADRP underwent repeated complete ophthalmologic evaluations which include best corrected visual acuity, slit lamp and fundus examination, full-field ERG and Goldmann kinetic perimetry. Blood samples were collected from all 8 affected individuals and 10 of 16 non affected members after informed consent. A genome-wide linkage analysis was performed with microsatellite markers from the ABI linkage mapping set 2.5. PROM1 exons and intron-exon junctions were screened by DHPLC and DNA with abnormal retention times were directly sequenced using the Big Dye sequencing kit 1.1.
First symptoms appeared between age 14 and 58 years with reading difficulties followed by photophobia, visual field narrowing and hemeralopia. The initial best corrected visual acuity varied between 1/60 and 1.0, but decreased dramatically within a mean follow-up period of 4 years, Bull’s eye maculopathy was observed in all of the examined patients, and progressed to macular atrophy in 5 of 6 examined patients at a mean age of 46 years. Osteoclastic pigmented peripheral retinopathy was noticed in 2 individuals. Visual field revealed concentric loss of sensibility and central scotoma in cases with severe maculopathy. ERG records in all 6 examined patients disclosed rod-cone dystrophy. Positive lod scores were obtained for markers D4S403 (3.3 at θ=0) and D4S419 (3.5 at θ=0). Screening of the PROML1 gene located in the linked interval revealed an R373C (CGC>TGC) mutation. The mutation segregated in all affected individuals and was never present in the non affected patients nor in 100 control individuals.
Prominin is a polytopic membrane protein. Within the retina, prominin is expressed in rod photoreceptor and is implied in the biogenesis of photoreceptive disks. The only PROML1 disease-causing mutation reported so far was associated with a unique Indian family affected with autosomal recessive retinal degeneration. The present study describes an autosomal dominant atypical inverse retinitis pigmentosa caused by PROML1 gene mutation and suggests that different mutations in PROMLl may be responsible for various phenotypes and distinct transmission modes.
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