Alternative splicing and retinal degeneration


  • M M Liu,

    1. Wilmer Eye Institute
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  • D J Zack

    Corresponding author
    1. Department of Molecular Biology and Genetics
    2. Department of Neuroscience
    3. McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    4. Institut de la Vision, Université Pierre et Marie Curie, Paris, France
    • Wilmer Eye Institute
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  • Nothing to declare.

Corresponding author: Donald Zack, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Smith Building—Room 3029, 400 N. Broadway, Baltimore, MD 21287, USA.

Tel.: (410) 502–5230;

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Alternative splicing is highly regulated in tissue-specific and development-specific patterns, and it has been estimated that 15% of disease-causing point mutations affect pre-mRNA splicing. In this review, we consider the cis-acting splice site and trans-acting splicing factor mutations that affect pre-mRNA splicing and contribute to retinal degeneration. Numerous splice site mutations have been identified in retinitis pigmentosa (RP) and various cone-rod dystrophies. Mutations in alternatively spliced retina-specific exons of the widely expressed RPGR and COL2A1 genes lead primarily to X-linked RP and ocular variants of Stickler syndrome, respectively. Furthermore, mutations in general pre-mRNA splicing factors, such as PRPF31, PRPF8, and PRPF3, predominantly cause autosomal dominant RP. These findings suggest an important role for pre-mRNA splicing in retinal homeostasis and the pathogenesis of retinal degenerative diseases. The development of novel therapeutic strategies to modulate aberrant splicing, including small molecule-based therapies, has the potential to lead to new treatments for retinal degenerative diseases.