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Mutations in a novel retina-specific gene cause autosomal dominant retinitis pigmentosa

Nature Genetics volume 22, pages 255–259 (1999)Cite this article

Abstract

Inherited retinal diseases are a common cause of visual impairment in children and young adults, often resulting in severe loss of vision in later life. The most frequent form of inherited retinopathy is retinitis pigmentosa (RP), with an approximate incidence of 1 in 3,500 individuals worldwide1,2. RP is characterized by night blindness and progressive degeneration of the midperipheral retina, accompanied by bone spicule-like pigmentary deposits and a reduced or absent electroretinogram (ERG). The disease process culminates in severe reduction of visual fields or blindness. RP is genetically heterogeneous, with autosomal dominant, autosomal recessive and X-linked forms. Here we have identified two mutations in a novel retina-specific gene from chromosome 8q that cause the RP1 form of autosomal dominant RP in three unrelated families. The protein encoded by this gene is 2,156 amino acids and its function is currently unknown, although the amino terminus has similarity to that of the doublecortin protein, whose gene (DCX) has been implicated in lissencephaly in humans17. Two families have a nonsense mutation in codon 677 of this gene (Arg677stop), whereas the third family has a nonsense mutation in codon 679 (Gln679stop). In one family, two individuals homozygous for the mutant gene have more severe retinal disease compared with heterozygotes.

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Figure 1: Gene and protein structure of RP1.
Figure 2: Sequence electropherograms of mutations found in three adRP families.
Figure 3: Pedigree and mutation screen of a consanguineous nuclear family in UCLA-RP01.
Figure 4: Expression of RP1 transcript in human tissues.

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Acknowledgements

We thank family members of UCLA-RP01 for participation, R. McInnes for retinal northern blots and P. Forsythe for technical assistance. This work was supported by grants from the Foundation Fighting Blindness and the George Gund Foundation, the William Stamps Farish Fund, the M.D. Anderson Foundation, the John S. Dunn Research Foundation, grant EY07142 from the National Eye Institute-National Institutes of Health (L.S.S., S.J.B. and S.P.D.), grant 5-FY98-0725 from the March of Dimes Birth Defects Foundation (J.Z.), a grant from the British Retinitis Pigmentosa Society and grant 035535/Z/96 from the Wellcome Trust (C.F.I.).

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Authors and Affiliations

  1. Human Genetics Center, School of Public Health,

    Lori S. Sullivan, Sara J. Bowne & Stephen P. Daiger

  2. Department of Ophthalmology and Visual Science, The University of Texas Health Science Center, 6901 Bertner Street, Houston, 77030, Texas, USA

    Lori S. Sullivan, Sara J. Bowne & Stephen P. Daiger

  3. Jules Stein Eye Institute, University of California , Los Angeles, California, USA

    John R. Heckenlively

  4. Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

    Jian Zuo

  5. South African National Bioinformatics Institute, University of the Western Cape, Belleville, South Africa

    Winston A. Hide

  6. Institute of Human Genetics, University Hospital Eppendorf , Hamburg, Germany

    Andreas Gal

  7. Biochemistry Department, University of Otago, Dunedin, New Zealand

    Michael Denton

  8. Molecular Medicine Unit, Leeds University, Leeds, UK

    Chris F. Inglehearn

  9. Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA

    Susan H. Blanton

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  1. Lori S. Sullivan
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Correspondence to Lori S. Sullivan.

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Sullivan, L., Heckenlively, J., Bowne, S. et al. Mutations in a novel retina-specific gene cause autosomal dominant retinitis pigmentosa. Nat Genet 22, 255–259 (1999). https://doi.org/10.1038/10314

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