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GJ Pauer, Q Xi, Z Yu, G Antinolo, K Zhang, SA Hagstrom; Screen For Mutations In The PROML1 Gene In 282 Patients With Retinitis Pigmentosa And Age-related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2002;43(13):802.
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Purpose: PROML1 is a member of the prominin family of 5-transmembrane cell surface glycoproteins. Murine prom is concentrated in the plasma membrane evaginations at the base of the outer segments of rod photoreceptors in the retina. A frame shift mutation in PROML1 has been identified as the cause of retinal degeneration in a consanguineous pedigree from India. Fundus examination of affected individuals show narrowed arteries, pigment deposits and macular degeneration. We investigated PROML1 as a candidate gene for autosomal recessive retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Methods: To date, a partial screen (24 of the 25 exons) for mutations in 138 unrelated patients with autosomal recessive RP, 97 unrelated patients with isolate RP, and 47 unrelated patients with AMD have been performed using exon-by-exon SSCP. Variant bands detected by SSCP were further analyzed by direct genomic sequencing. Results: Three missense sequence changes (Ser19Ala, Val449Met, and Asp537Gly) were identified in patients with RP and five isocoding changes (Leu5Leu, Thr43Thr, Leu76Leu, Ala262Ala, Ser698Ser) were found in patients with RP and AMD. In addition, nine intronic polymorphisms were identified. None of the isocoding or intronic changes alter a splice site. Cosegregation analysis is pending in the respective families with RP to help determine whether the observed missense sequence anomalies are pathogenic. Conclusion: We report eight unique sequence changes in the coding region of PROML1 in patients with RP and AMD. The possible pathogenic role of these changes is under investigation. We are proceeding with an evaluation of the remaining exon in these patients and an evaluation of all exons in additional patients with allied diseases.
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