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Next-generation sequencing-based molecular diagnosis of 82 retinitis pigmentosa probands from Northern Ireland

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Abstract

Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by progressive photoreceptor degeneration. An accurate molecular diagnosis is essential for disease characterization and clinical prognoses. A retinal capture panel that enriches 186 known retinal disease genes, including 55 known RP genes, was developed. Targeted next-generation sequencing was performed for a cohort of 82 unrelated RP cases from Northern Ireland, including 46 simplex cases and 36 familial cases. Disease-causing mutations were identified in 49 probands, including 28 simplex cases and 21 familial cases, achieving a solving rate of 60 %. In total, 65 pathogenic mutations were found, and 29 of these were novel. Interestingly, the molecular information of 12 probands was neither consistent with their initial inheritance pattern nor clinical diagnosis. Further clinical reassessment resulted in a refinement of the clinical diagnosis in 11 patients. This is the first study to apply next-generation sequencing-based, comprehensive molecular diagnoses to a large number of RP probands from Northern Ireland. Our study shows that molecular information can aid clinical diagnosis, potentially changing treatment options, current family counseling and management.

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Acknowledgments

We gratefully acknowledge all participating patients and their family members. R.C. is supported by grants from Retinal Research Foundation, Foundation Fighting Blindness (BR-GE-0613-0618-BCM) and the National Eye Institute (R01EY022356, R01EY018571). F.W. is supported by predoctoral fellowship: The Burroughs Wellcome Fund, The Houston Laboratory and Population Sciences Training Program in Gene Environment Interaction.

Conflict of interest

The authors declare no conflict of interest.

Ethical standards

This research was conducted in accordance with the Tenets of the declaration of Helsinki. Ethical permission was granted through ORECNI and all patients gave written consent to participate in the study.

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Authors and Affiliations

  1. Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA

    Li Zhao & Rui Chen

  2. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA

    Li Zhao, Feng Wang, Hui Wang, Yumei Li, Keqing Wang, Jacques E. Zaneveld, Lichun Jiang, Zachry T. Soens & Rui Chen

  3. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA

    Feng Wang, Hui Wang, Yumei Li, Keqing Wang, Jacques E. Zaneveld, Lichun Jiang, Zachry T. Soens & Rui Chen

  4. Centre for Experimental Medicine, Queen’s University Belfast, Clinical ICS-A, Belfast, BT12 6BA, UK

    Sharon Alexander, Philip Earle, David Simpson & Giuliana Silvestri

  5. Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L69 3GA, UK

    Colin E. Willoughby

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  1. Li Zhao
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Corresponding authors

Correspondence to Giuliana Silvestri or Rui Chen.

Additional information

L. Zhao and F. Wang contributed equally to this work.

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Zhao, L., Wang, F., Wang, H. et al. Next-generation sequencing-based molecular diagnosis of 82 retinitis pigmentosa probands from Northern Ireland. Hum Genet 134, 217–230 (2015). https://doi.org/10.1007/s00439-014-1512-7

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