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Mutations in a gene encoding a new oxygen-regulated photoreceptor protein cause dominant retinitis pigmentosa

Abstract

The autosomal dominant retinitis pigmentosa (RP) locus, designated RP1, has been mapped through linkage studies to a 4-cM interval at 8q11–13. Here we describe a new photoreceptor-specific gene that maps in this interval and whose expression is modulated by retinal oxygen levels in vivo. This gene consists of at least 4 exons that encode a predicted protein of 2,156 amino acids. A nonsense mutation at codon 677 of this gene is present in approximately 3% of cases of dominant RP in North America. We also detected two deletion mutations that cause frameshifts and introduce premature termination codons in three other families with dominant RP. Our data suggest that mutations in this gene cause dominant RP, and that the encoded protein has an important but unknown role in photoreceptor biology.

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Figure 1: Identification and expression of mouse Rp1.
Figure 2: Regulation of Rp1 expression during development and identification of human RP1.
Figure 3: The predicted human ORP1 protein sequence.
Figure 4: Chromosomal location of the human RP1 gene.
Figure 5: The Arg677Ter mutation in RP1 patients.
Figure 6: The Leu762(5-bp del) and Asn763(4-bp del) mutations.
Figure 7: Fundus photograph of an affected patient.

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Acknowledgements

We thank S. Adams, C. Bresilla, J. Grimsby, R. Reichert and R. Sullivan for assistance; E. Engle, A. Beggs and L. Kunkel for discussions and encouragement; and J. Knoll for FISH analysis. This work was supported by grants from the NIH (EY12910, EY08689 and EY00169), the Fight for Sight Research Division of Prevent Blindness America, the Foundation Fighting Blindness and Children's Hospital, Boston.

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Correspondence to Eric A. Pierce.

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Pierce, E., Quinn, T., Meehan, T. et al. Mutations in a gene encoding a new oxygen-regulated photoreceptor protein cause dominant retinitis pigmentosa. Nat Genet 22, 248–254 (1999). https://doi.org/10.1038/10305

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