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EYS-Associated Sector Retinitis Pigmentosa

  • Genetics
  • Published:
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Abstract

Purpose

Sector retinitis pigmentosa (RP) is a rare form of rod-cone degeneration typically associated with mutations in the RHO gene. We describe six unrelated patients presenting with this atypical phenotype in association with biallelic mutations in EYS gene.

Methods

Multinational, multicentre cross-sectional case series. Patients with biallelic disease-causing variants in EYS and a clinical diagnosis of sector RP were recruited from specialized centres in Portugal and Brazil. All patients underwent a comprehensive ophthalmologic examination complemented by deep phenotyping. Peripheral blood samples were collected from all probands and available relatives for genetic analysis. Genetic counselling was provided to all subjects.

Results

Seven disease-causing variants (4 pathogenic; 3 likely pathogenic) were identified in 6 unrelated female patients. Best-corrected visual acuity ranged from 75 to 85 ETDRS letters. All eyes showed bilateral and symmetrical areas of outer retinal atrophy distributed along the inferior vascular arcades and extending temporally and/or nasally in a crescent-shaped pattern. On fundus autofluorescence (AF), a foveal-sparing curvilinear band of hyperAF encroaching the optic nerve head and extending temporally was seen in 4 patients. The remaining 2 presented bilateral and symmetrical patches of hypoAF inside crescent-shaped areas of hyperAF along the inferior temporal vascular arcade. Visual field testing revealed superior visual field defects of varying extents, always in close association with the fundus AF findings.

Conclusions

Even though EYS has only recently been listed as a cause of the sector RP phenotype, we believe that this presentation is not infrequent and should be considered an important differential for sector RP.

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References

  1. Massof Rw, Finkelstein D (1979) Vision threshold profiles in sector retinitis pigmentosa. Arch Ophthalmol 97(10):1899–1904

  2. Van Woerkom C, Ferrucci S (2005) Sector retinitis pigmentosa. Optometry 76(5):309–317

  3. Napier Ml, Durga D, Wolsley Cj et al (2015) Mutational analysis of the rhodopsin gene in sector retinitis pigmentosa. Ophthalmic Genet 36(3):239–243

  4. Coussa Rg, Basali D, Maeda A et al (2019) Sector retinitis pigmentosa: report of ten cases and a review of the literature. Mol Vis 25:869–889

  5. Xiao T, Xu K, Zhang X et al (2019) Sector retinitis pigmentosa caused by mutations of the Rho gene. Eye (Lond) 33(4):592–599

  6. Oliveira Ma, Neves E, Marques Jp (2020) Genetic, anatomical, and functional correlation of sector retinitis pigmentosa. Jama Ophthalmol 138(6):E193133

  7. Bisantis C (1971) [G.B. Bietti's sectorial pigmentary retinopathy. contribution to the knowledge of its various clinical aspects]. Ann Ocul (Paris) 204(9):907–54

  8. Xt Nguyen, Talib M, Van Cauwenbergh C et al (2020) Clinical characteristics and natural history of Rho-associated retinitis pigmentosa: a long-term follow-up study. Retina 41(1):213–223

  9. Ramon E, Cordomi A, Aguila M et al (2014) Differential light-induced responses in sectorial inherited retinal degeneration. J Biol Chem 289(52):35918–35928

  10. Georgiou M, Ps Grewal, Narayan A et al (2020) Sector Retinitis pigmentosa: extending the molecular genetics basis and elucidating the natural history. Am J Ophthalmol 221:299–310

  11. Saihan Z, StabejPle Q, Robson Ag et al (2011) Mutations in the Ush1c gene associated with sector retinitis pigmentosa and hearing loss. Retina 31(8):1708–1716

  12. Branson Sv, Mcclintic Ji, Stamper Th et al (2016) Sector retinitis pigmentosa associated with novel compound heterozygous mutations of Cdh23. Ophthalmic Surg Lasers Imaging Retina 47(2):183–186

  13. Sato M, Oshika T, Kaji Y et al (2004) A novel homozygous Gly107arg mutation in the Rdh5 gene in a japanese patient with fundus albipunctatus with sectorial retinitis pigmentosa. Ophthalmic Res 36(1):43–50

  14. Nakamachi Y, Nakamura M, Fujii S et al (1998) Oguchi disease with sectoral retinitis pigmentosa harboring adenine deletion at position 1147 in the arrestin gene. Am J Ophthalmol 125(2):249–251

  15. Pappalardo J, Heath Jeffery RC, Thompson JA et al (2021) Progressive sector retinitis pigmentosa due to C.440g>T mutation in SAG in an Australian family. Ophthalmic Genet 42(1):62–70

  16. Arai Y, Maeda A, Hirami Y et al (2015) Retinitis pigmentosa with eys mutations is the most prevalent inherited retinal dystrophy in Japanese populations. J Ophthalmol 2015:819760

  17. Audo I, Ja S, Mohand-Said S et al (2010) Eys is a major gene for rod-cone dystrophies in France. Hum Mutat 31(5):E1406–E1435

  18. Barragan I, Borrego S, Ji P et al (2010) Mutation spectrum of eys in spanish patients with autosomal recessive retinitis pigmentosa. Hum Mutat 31(11):E1772–E1800

  19. Yang L, Fujinami K, Ueno S et al (2020) Genetic spectrum of eys-associated retinal disease in a large Japanese cohort: identification of disease-associated variants with relatively high allele frequency. Sci Rep 10(1):5497

  20. Abd El-Aziz Mm, Barragan I, O’driscoll Ca et al (2008) Encoding an ortholog of drosophila spacemaker, is mutated in autosomal recessive retinitis pigmentosa. Nat Genet 40(11):1285–1287

  21. Collin Rw, Littink Kw, Klevering Bj et al (2008) Identification of A 2 Mb human ortholog of drosophila eyes shut/spacemaker that is mutated in patients with retinitis pigmentosa. Am J Hum Genet 83(5):594–603

  22. Pierrache Lhm, Messchaert M, Thiadens A et al (2019) Extending the spectrum of eys-associated retinal disease to macular dystrophy. Invest Ophthalmol Vis Sci 60(6):2049–2063

  23. Sengillo Jd, Lee W, Nagasaki T et al (2018) A distinct phenotype of eyes shut homolog (eys)-retinitis pigmentosa is associated with variants near the c-terminus. Am J Ophthalmol 190:99–112

  24. Mucciolo Dp, Sodi A, Passerini I et al (2018) Fundus phenotype in retinitis pigmentosa associated with eys mutations. Ophthalmic Genet 39(5):589–602

  25. Marques Jp, Carvalho Al, Henriques J et al (2020) Design, development and deployment of a web-based interoperable registry for inherited retinal dystrophies in Portugal: the ird-pt. Orphanet J Rare Dis 15(1):304

  26. Mcculloch Dl, Marmor Mf, Brigell Mg et al (2015) Iscev standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 130(1):1–12

  27. Fbo Porto, Em Jones, Branch J et al (2017) Molecular screening of 43 Brazilian families diagnosed with leber congenital amaurosis or early-onset severe retinal dystrophy. Genes (Basel) 8(12):355

  28. Giambene B, Verdina T, Pennino M et al (2020) Multifocal electroretinographic responses in sector retinitis pigmentosa. Int Ophthalmol 40(3):703–708

  29. Bandah-Rozenfeld D, Littink Kw, Ben-Yosef T et al (2010) Novel null mutations in the eys gene are a frequent cause of autosomal recessive retinitis pigmentosa in the Israeli population. Invest Ophthalmol Vis Sci 51(9):4387–4394

  30. Cundy O, Broadgate S, Halford S et al (2020) Genetic and clinical findings in an ethnically diverse retinitis pigmentosa cohort associated with pathogenic variants in eys. Eye (Lond) 35(5):1440–1449

  31. Db Mcguigan, Heon E, Av Cideciyan et al (2017) Eys mutations causing autosomal recessive retinitis pigmentosa: changes of retinal structure and function with disease progression. Genes (Basel) 8(7):178

  32. Habibi I, Chebil A, Falfoul Y et al (2016) Identifying mutations in tunisian families with retinal dystrophy. Sci Rep 6(1):37455

  33. Gonzalez-Del Pozo M, Borrego S, Barragan I et al (2011) Mutation screening of multiple genes in Spanish patients with autosomal recessive retinitis pigmentosa by targeted resequencing. PLoS ONE 6(12):E27894

  34. Schwartz L, Boelle Py, D’hermies F et al (2003) Blue light dose distribution and retinitis pigmentosa visual field defects: an hypothesis. Med Hypotheses 60(5):644–649

  35. Alfano G, Kruczek Pm, Shah Az et al (2016) Eys is a protein associated with the ciliary axoneme in rods and cones. PLoS ONE 11(11):E0166397

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Author information

Authors and Affiliations

  1. Ophthalmology Unit, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal

    João Pedro Marques, Emmanuel Neves, Joaquim Murta & Rufino Silva

  2. University Clinic of Ophthalmology, Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal

    João Pedro Marques, Joaquim Murta & Rufino Silva

  3. Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal

    João Pedro Marques, Ana Luísa Carvalho, Joaquim Murta, Jorge Saraiva & Rufino Silva

  4. Centro de Responsabilidade Integrado de Oftalmologia (CRIO), Centro Hospitalar e Universitário de Coimbra (CHUC), Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal

    João Pedro Marques

  5. INRET Clínica e Centro de Pesquisa, Belo Horizonte, Minas Gerais, 30150270, Brazil

    Fernanda Belga Ottoni Porto & Shirley Aparecida Madureira Sampaio

  6. Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, IEP/SCBH, Belo Horizonte, Minas Gerais, 30150290, Brazil

    Fernanda Belga Ottoni Porto

  7. Centro Oftalmológico de Minas Gerais, COMG, Belo Horizonte, Minas Gerais, 30150290, Brazil

    Fernanda Belga Ottoni Porto

  8. Medical Genetics Unit, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal

    Ana Luísa Carvalho & Jorge Saraiva

  9. University Clinic of Medical Genetics, Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal

    Ana Luísa Carvalho

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

    Rui Chen

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

    Rui Chen

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

    Rui Chen

  13. University Clinic of Pediatrics, Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal

    Jorge Saraiva

Authors
  1. João Pedro Marques
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  2. Fernanda Belga Ottoni Porto
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  3. Ana Luísa Carvalho
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  4. Emmanuel Neves
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  6. Shirley Aparecida Madureira Sampaio
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  7. Joaquim Murta
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  9. Rufino Silva
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Corresponding author

Correspondence to João Pedro Marques.

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Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the HREC of Centro Hospitalar e Universitário de Coimbra (CHUC) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Supplementary Fig. 1

Full-field electroretinogram (ffERG) of Patients 4, 5 and 6. On patients 4 and 5, bilateral marginally recordable scotopic and photopic responses were recorded. Patient 6 presented a subnormal scotopic and photopic ffERG. (PNG 1308 kb)

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Marques, J.P., Porto, F.B.O., Carvalho, A.L. et al. EYS-Associated Sector Retinitis Pigmentosa. Graefes Arch Clin Exp Ophthalmol 260, 1405–1413 (2022). https://doi.org/10.1007/s00417-021-05411-w

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  • DOI: https://doi.org/10.1007/s00417-021-05411-w

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