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A novel MERTK mutation causing retinitis pigmentosa

  • Genetics
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

Retinitis pigmentosa (RP) is a genetically heterogeneous inherited retinal dystrophy. To date, over 80 genes have been implicated in RP. However, the disease demonstrates significant locus and allelic heterogeneity not entirely captured by current testing platforms. The purpose of the present study was to characterize the underlying mutation in a patient with RP without a molecular diagnosis after initial genetic testing.

Methods

Whole-exome sequencing of the affected proband was performed. Candidate gene mutations were selected based on adherence to expected genetic inheritance pattern and predicted pathogenicity. Sanger sequencing of MERTK was completed on the patient’s unaffected mother, affected brother, and unaffected sister to determine genetic phase.

Results

Eight sequence variants were identified in the proband in known RP-associated genes. Sequence analysis revealed that the proband was a compound heterozygote with two independent mutations in MERTK, a novel nonsense mutation (c.2179C > T) and a previously reported missense variant (c.2530C > T). The proband’s affected brother also had both mutations. Predicted phase was confirmed in unaffected family members.

Conclusion

Our study identifies a novel nonsense mutation in MERTK in a family with RP and no prior molecular diagnosis. The present study also demonstrates the clinical value of exome sequencing in determining the genetic basis of Mendelian diseases when standard genetic testing is unsuccessful.

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Acknowledgements

The authors extend our deep gratitude to the proband and his family. We also thank Vaiva Liakaite at the University of Illinois at Chicago’s DNA Services Facility and the sequencing center at BGI for assisting with the present study. Lastly, the authors thank Darshana Patel for assisting with the coordination of this study.

Author information

Author notes

  1. Hasenin Al-khersan and Kaanan P. Shah contributed equally to this work.

Authors and Affiliations

  1. Pritzker School of Medicine, The University of Chicago, Chicago, IL, 60637, USA

    Hasenin Al-khersan

  2. Section of Genetic Medicine, The University of Chicago, Chicago, IL, 60637, USA

    Kaanan P. Shah

  3. Argonne National Laboratory – Computation Institute, The University of Chicago, Chicago, IL, 60637, USA

    Segun C. Jung, Alex Rodriguez & Ravi K. Madduri

  4. Grassi Retina, Naperville, IL, 60564, USA

    Michael A. Grassi

  5. Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1012 95th St., Suite 9, Naperville, IL, 60564, USA

    Michael A. Grassi

Authors
  1. Hasenin Al-khersan
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  2. Kaanan P. Shah
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  3. Segun C. Jung
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  4. Alex Rodriguez
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Corresponding author

Correspondence to Michael A. Grassi.

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Funding

This report was supported by funding from Search for Vision, R01EY023644, NEI core grant EY001792, and Research to Prevent Blindness (departmental support). The sponsor had no role in the design or conduct of this research.

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Al-khersan, H., Shah, K.P., Jung, S.C. et al. A novel MERTK mutation causing retinitis pigmentosa. Graefes Arch Clin Exp Ophthalmol 255, 1613–1619 (2017). https://doi.org/10.1007/s00417-017-3679-9

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  • DOI: https://doi.org/10.1007/s00417-017-3679-9

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