Human Genetics

, Volume 134, Issue 2, pp 217–230 | Cite as

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

  • Li Zhao
  • Feng Wang
  • Hui Wang
  • Yumei Li
  • Sharon Alexander
  • Keqing Wang
  • Colin E. Willoughby
  • Jacques E. Zaneveld
  • Lichun Jiang
  • Zachry T. Soens
  • Philip Earle
  • David Simpson
  • Giuliana SilvestriEmail author
  • Rui ChenEmail author
Original Investigation


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.


Retinitis Pigmentosa Retinal Disease Usher Syndrome CDH23 Mutation Retinitis Pigmentosa Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



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.

Supplementary material

439_2014_1512_MOESM1_ESM.pdf (574 kb)
Supplementary material 1 (PDF 573 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Li Zhao
    • 1
    • 2
  • Feng Wang
    • 2
    • 3
  • Hui Wang
    • 2
    • 3
  • Yumei Li
    • 2
    • 3
  • Sharon Alexander
    • 4
  • Keqing Wang
    • 2
    • 3
  • Colin E. Willoughby
    • 5
  • Jacques E. Zaneveld
    • 2
    • 3
  • Lichun Jiang
    • 2
    • 3
  • Zachry T. Soens
    • 2
    • 3
  • Philip Earle
    • 4
  • David Simpson
    • 4
  • Giuliana Silvestri
    • 4
    Email author
  • Rui Chen
    • 1
    • 2
    • 3
    Email author
  1. 1.Structural and Computational Biology and Molecular BiophysicsBaylor College of MedicineHoustonUSA
  2. 2.Human Genome Sequencing CenterBaylor College of MedicineHoustonUSA
  3. 3.Department of Molecular and Human GeneticsBaylor College of MedicineHoustonUSA
  4. 4.Centre for Experimental MedicineQueen’s University Belfast, Clinical ICS-ABelfastUK
  5. 5.Department of Eye and Vision Science, Institute of Ageing and Chronic DiseaseUniversity of LiverpoolLiverpoolUK

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