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Phenotypic expansion and progression of SPATA7-associated retinitis pigmentosa

  • Clinical Case Report
  • Published:
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Abstract

Purpose

To report an unusual phenotype of retinitis pigmentosa (RP) caused by compound heterozygous mutations in SPATA7, and describe the progression over a two year follow-up period.

Methods

Retrospective case study.

Results

A 63-year-old man with a long history of nyctalopia, progressive visual field constriction, and a recent subacute decrease in visual acuity of the left eye presented for evaluation of a suspected retinal degeneration. Multimodal retinal imaging and functional assessment with full-field electroretinogram suggested a severe rod-cone dysfunction masquerading as a choroideremia-like phenotype. A vitreous opacity was found to explain recent changes in the left eye and a 25-guage vitrectomy and membrane peel was performed, yielding no change in visual acuity. Whole-exome sequencing revealed compound heterozygous variants in SPATA7 that were predicted to be pathogenic.

Conclusions

Compound heterozygous c.1100A > G, p.(Y367C) and c.1102_1103delCT, p.(L368Efs*4) variants in SPATA7 manifest as an unusual RP phenotype in this case, showing extensive choroidal sclerosis and retinal pigment epithelium (RPE) atrophy with evidence of progression over two years on multimodal imaging.

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References

  1. Sengillo JD, Justus S, Cabral T, Tsang SH (2017) Correction of monogenic and common retinal disorders with gene therapy. Genes (Basel). https://doi.org/10.3390/genes8020053

    Google Scholar 

  2. Sengillo JD, Justus S, Tsai YT, Cabral T, Tsang SH (2016) Gene and cell-based therapies for inherited retinal disorders: an update. Am J Med Genet C Semin Med Genet 172(4):349–366. https://doi.org/10.1002/ajmg.c.31534

    Article  PubMed  Google Scholar 

  3. Berson EL (1993) Retinitis pigmentosa. the Friedenwald Lecture. Invest Ophthalmol Vis Sci 34(5):1659–1676

    CAS  PubMed  Google Scholar 

  4. Hamel C (2006) Retinitis pigmentosa. Orphanet J Rare Dis 1:40. https://doi.org/10.1186/1750-1172-1-40

    Article  PubMed  PubMed Central  Google Scholar 

  5. Broadgate S, Yu J, Downes SM, Halford S (2017) Unravelling the genetics of inherited retinal dystrophies: past, present and future. Prog Retin Eye Res. https://doi.org/10.1016/j.preteyeres.2017.03.003

    PubMed  Google Scholar 

  6. Zhang X, Liu H, Zhang Y, Qiao Y, Miao S, Wang L, Zhang J, Zong S, Koide SS (2003) A novel gene, RSD-3/HSD-3.1, encodes a meiotic-related protein expressed in rat and human testis. J Mol Med (Berl) 81(6):380–387. https://doi.org/10.1007/s00109-003-0434-y

    Article  CAS  Google Scholar 

  7. Eblimit A, Nguyen TM, Chen Y, Esteve-Rudd J, Zhong H, Letteboer S, Van Reeuwijk J, Simons DL, Ding Q, Wu KM, Li Y, Van Beersum S, Moayedi Y, Xu H, Pickard P, Wang K, Gan L, Wu SM, Williams DS, Mardon G, Roepman R, Chen R (2015) Spata7 is a retinal ciliopathy gene critical for correct RPGRIP1 localization and protein trafficking in the retina. Hum Mol Genet 24(6):1584–1601. https://doi.org/10.1093/hmg/ddu573

    Article  CAS  PubMed  Google Scholar 

  8. Zhong H, Eblimit A, Moayedi Y, Boye SL, Chiodo VA, Chen Y, Li Y, Nichols RM, Hauswirth WW, Chen R, Mardon G (2015) AAV8(Y733F)-mediated gene therapy in a Spata7 knockout mouse model of Leber congenital amaurosis and retinitis pigmentosa. Gene Ther 22(8):619–627. https://doi.org/10.1038/gt.2015.42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mackay DS, Ocaka LA, Borman AD, Sergouniotis PI, Henderson RH, Moradi P, Robson AG, Thompson DA, Webster AR, Moore AT (2011) Screening of SPATA7 in patients with Leber congenital amaurosis and severe childhood-onset retinal dystrophy reveals disease-causing mutations. Invest Ophthalmol Vis Sci 52(6):3032–3038. https://doi.org/10.1167/iovs.10-7025

    Article  CAS  PubMed  Google Scholar 

  10. Perrault I, Hanein S, Gerard X, Delphin N, Fares-Taie L, Gerber S, Pelletier V, Merce E, Dollfus H, Puech B, Defoort-Dhellemmes S, Petersen MD, Zafeiriou D, Munnich A, Kaplan J, Roche O, Rozet JM (2010) Spectrum of SPATA7 mutations in Leber congenital amaurosis and delineation of the associated phenotype. Hum Mutat 31(3):E1241–E1250. https://doi.org/10.1002/humu.21203

    Article  CAS  PubMed  Google Scholar 

  11. Wang H, den Hollander AI, Moayedi Y, Abulimiti A, Li Y, Collin RW, Hoyng CB, Lopez I, Abboud EB, Al-Rajhi AA, Bray M, Lewis RA, Lupski JR, Mardon G, Koenekoop RK, Chen R (2009) Mutations in SPATA7 cause Leber congenital amaurosis and juvenile retinitis pigmentosa. Am J Hum Genet 84(3):380–387. https://doi.org/10.1016/j.ajhg.2009.02.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mayer AK, Mahajnah M, Zobor D, Bonin M, Sharkia R, Wissinger B (2015) Novel homozygous large deletion including the 5’ part of the SPATA7 gene in a consanguineous Israeli Muslim Arab family. Mol Vis 21:306–315

    CAS  PubMed  PubMed Central  Google Scholar 

  13. McCulloch DL, Marmor MF, Brigell MG, Hamilton R, Holder GE, Tzekov R, Bach M (2015) Erratum to: ISCEV Standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 131(1):81–83. https://doi.org/10.1007/s10633-015-9504-z

    Article  PubMed  Google Scholar 

  14. McCulloch DL, Marmor MF, Brigell MG, Hamilton R, Holder GE, Tzekov R, Bach M (2015) ISCEV Standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 130(1):1–12. https://doi.org/10.1007/s10633-014-9473-7

    Article  PubMed  Google Scholar 

  15. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, Laboratory Quality Assurance Committee ACMG (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–424. https://doi.org/10.1038/gim.2015.30

    Article  PubMed  PubMed Central  Google Scholar 

  16. Consugar MB, Navarro-Gomez D, Place EM, Bujakowska KM, Sousa ME, Fonseca-Kelly ZD, Taub DG, Janessian M, Wang DY, Au ED, Sims KB, Sweetser DA, Fulton AB, Liu Q, Wiggs JL, Gai X, Pierce EA (2015) Panel-based genetic diagnostic testing for inherited eye diseases is highly accurate and reproducible and more sensitive for variant detection than exome sequencing. Genet Med 17(4):253–261. https://doi.org/10.1038/gim.2014.172

    Article  CAS  PubMed  Google Scholar 

  17. Berson EL (2007) Long-term visual prognoses in patients with retinitis pigmentosa: the Ludwig von Sallmann lecture. Exp Eye Res 85(1):7–14. https://doi.org/10.1016/j.exer.2007.03.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Parmeggiani F, Sato G, De Nadai K, Romano MR, Binotto A, Costagliola C (2011) Clinical and rehabilitative management of retinitis pigmentosa: up-to-date. Curr Genom 12(4):250–259. https://doi.org/10.2174/138920211795860125

    Article  CAS  Google Scholar 

  19. Ma KK, Lin J, Boudreault K, Chen RW, Tsang SH (2017) Phenotyping choroideremia and its carrier state with multimodal imaging techniques. Retin Cases Brief Rep 11(Suppl 1):S178–S181. https://doi.org/10.1097/ICB.0000000000000419

    Article  PubMed  PubMed Central  Google Scholar 

  20. Jayasundera T, Branham KEH, Othman M, Rhoades WR, Karoukis AJ, Khanna H, Swaroop A, Heckenlively JR (2010) The RP2 phenotype and pathogenic correlations in X-linked retinitis pigmentosa. Arch Ophthalmol 128(7):915–923. https://doi.org/10.1001/archophthalmol.2010.122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author’s contributions

JDS and WL collected and interpreted patient data and images, and composed the manuscript. CGB and VJ performed and interpreted genetic analyses. SHT conceived the experimental design and approved the final interpretation of the data.

Funding

Jonas Children’s Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory are supported by the National Institutes of Health (5P30EY019007, R01EY018213, R01EY024698, R01EY026682, R21AG050437), National Cancer Institute Core (5P30CA013696), the Research to Prevent Blindness (RPB) Physician-Scientist Award, unrestricted funds from RPB, New York, NY, USA. J.D.S is supported by the RPB Medical Student Eye Research Fellowship. S.H.T. is a member of the RD-CURE Consortium and is supported by the Tistou and Charlotte Kerstan Foundation, the Schneeweiss Stem Cell Fund, New York State (C029572), the Foundation Fighting Blindness New York Regional Research Center Grant (C-NY05-0705-0312), the Crowley Family Fund, and the Gebroe Family Foundation.

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Authors and Affiliations

  1. Jonas Children’s Vision Care, and Bernard & Shirlee Brown Glaucoma Laboratory, New York, NY, USA

    Jesse D. Sengillo & Stephen H. Tsang

  2. Department of Ophthalmology, Columbia University, New York, NY, USA

    Jesse D. Sengillo, Winston Lee & Stephen H. Tsang

  3. State University of New York Downstate Medical Center, Brooklyn, NY, USA

    Jesse D. Sengillo

  4. Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA

    Colleen G. Bilancia, Vaidehi Jobanputra & Stephen H. Tsang

  5. Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Stephen H. Tsang

Authors
  1. Jesse D. Sengillo
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  2. Winston Lee
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  3. Colleen G. Bilancia
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  4. Vaidehi Jobanputra
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  5. Stephen H. Tsang
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Corresponding author

Correspondence to Stephen H. Tsang.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Informed consent

The data presented in this study, including images and genetic testing results, are not identifiable to individual patients. For this type of study, formal consent is not required.

Ethics 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 Declaration of Helsinki and its later amendments or comparable ethical standards. Research involving the use of animals was not performed in this study.

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Sengillo, J.D., Lee, W., Bilancia, C.G. et al. Phenotypic expansion and progression of SPATA7-associated retinitis pigmentosa. Doc Ophthalmol 136, 125–133 (2018). https://doi.org/10.1007/s10633-018-9626-1

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  • DOI: https://doi.org/10.1007/s10633-018-9626-1

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