Novel clinical findings in autosomal recessive NR2E3-related retinal dystrophy

  • Vittoria Murro
  • Dario Pasquale MuccioloEmail author
  • Andrea Sodi
  • Ilaria Passerini
  • Dario Giorgio
  • Gianni Virgili
  • Stanislao Rizzo
Retinal Disorders



To evaluate the clinical phenotype of autosomal recessive NR2E3-related retinal dystrophy.


We retrospectively studied 11 patients carrying out at least 2 NR2E3 mutations; they had undergone comprehensive ophthalmological examination, fundus photography, optical coherence tomography, electrophysiological testing, and visual field at the Regional Reference Center for Hereditary Retinal Degenerations of the Eye Clinic in Florence.


Five females and six males with a diagnosis of NR2E3-related retinal dystrophy were included in the study. All patients complained of nyctalopia. Visual acuity ranged from 0.00 logMAR to hand motion. Two patients presented bull’s eye maculopathy, and one of these was characterized by a triple hyper-autofluorescent ring at the fundus autofluorescence examination. Three patients showed small yellowish dots and spots at the mid-periphery. One patient was characterized by widespread subretinal drusenoid deposits (SDD) at the posterior pole. Four patients showed vitreous abnormalities. Optical coherence tomography (OCT) examinations detected variable degrees of abnormal retinal lamination and schitic changes. Seven patients were compound heterozygous and four were homozygous for mutations in NR2E3.


Our study confirmed high variable phenotype in autosomal recessive NR2E3-related retinal dystrophy. Bull’s eye maculopathy, subretinal drusenoid deposits, and foveal hypoplasia represent novel clinical findings in NR2E3-related retinal dystrophy. Macular involvement was detectable in all the patients, and the abnormal foveal avascular zone (FAZ) supports the role of NR2E3 in retinal development.


NR2E3 Retinal dystrophy Subretinal drusenoid deposits Foveal hypoplasia Autosomal recessive disease Retinitis pigmentosa Goldmann-Favre 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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. For this type of study, formal consent is not required.


  1. 1.
    Kobayashi M, Takezawa S, Hara K, Yu RT, Umesono Y, Agata K, Taniwaki M, Yasuda K, Umesono K (1999) Identification of a photoreceptor cell-specific nuclear receptor. Proc Natl Acad Sci U S A 96(9):4814–4819CrossRefGoogle Scholar
  2. 2.
    Peng GH, Ahmad O, Ahmad F, Liu J, Chen S (2005) The photoreceptor-specific nuclear receptor Nr2e3 interacts with Crx and exerts opposing effects on the transcription of rod versus cone genes. Hum Mol Genet 14(6):747–764CrossRefGoogle Scholar
  3. 3.
    Haider NB, Demarco P, Nystuen AM, Huang X, Smith RS, McCall MA, Naggert JK, Nishina PM (2006) The transcription factor Nr2e3 functions in retinal progenitors to suppress cone cell generation. Vis Neurosci 23(6):917–929CrossRefGoogle Scholar
  4. 4.
    Milam AH, Rose L, Cideciyan AV, Barakat MR, Tang WX, Gupta N, Aleman TS, Wright AF, Stone EM, Sheffield VC, Jacobson SG (2002) The nuclear receptor NR2E3 plays a role in human retinal photoreceptor differentiation and degeneration. Proc Natl Acad Sci U S A 99(1):473–478CrossRefGoogle Scholar
  5. 5.
    Jacobson SG, Sumaroka A, Aleman TS, Cideciyan AV, Schwartz SB, Roman AJ, McInnes RR, Sheffield VC, Stone EM, Swaroop A, Wright AF (2004) Nuclear receptor NR2E3 gene mutations distort human retinal laminar architecture and cause an unusual degeneration. Hum Mol Genet 13(17):1893–1902CrossRefGoogle Scholar
  6. 6.
    Sharon D, Sandberg MA, Caruso RC, Berson EL, Dryja TP (2003) Shared mutations in NR2E3 in enhanced S-cone syndrome, Goldmann-Favre syndrome, and many cases of clumped pigmentary retinal degeneration. Arch Ophthalmol 121(9):1316–1323CrossRefGoogle Scholar
  7. 7.
    Gerber S, Rozet JM, Takezawa SI, dos Santos LC, Lopes L, Gribouval O, Penet C, Perrault I, Ducroq D, Souied E, Jeanpierre M, Romana S, Frézal J, Ferraz F, Yu-Umesono R, Munnich A, Kaplan J (2000) The photoreceptor cell-specific nuclear receptor gene (PNR) accounts for retinitis pigmentosa in the Crypto-Jews from Portugal (Marranos), survivors from the Spanish inquisition. Hum Genet 107(3):276–284CrossRefGoogle Scholar
  8. 8.
    Coppieters F, Leroy BP, Beysen D, Hellemans J, De Bosscher K, Haegeman G, Robberecht K, Wuyts W, Coucke PJ, De Baere E (2007) Recurrent mutation in the first zinc finger of the orphan nuclear receptor NR2E3 causes autosomal dominant retinitis pigmentosa. Am J Hum Genet 81(1):147–157CrossRefGoogle Scholar
  9. 9.
    Pachydaki SI, Klaver CC, Barbazetto IA, Roy MS, Gouras P, Allikmets R, Yannuzzi LA (2009) Phenotypic features of patients with NR2E3 mutations. Arch Ophthalmol 127(1):71–75CrossRefGoogle Scholar
  10. 10.
    Bandah D, Merin S, Ashhab M, Banin E, Sharon D (2009) The spectrum of retinal diseases caused by NR2E3 mutations in Israeli and Palestinian patients. Arch Ophthalmol 127(3):297–302CrossRefGoogle Scholar
  11. 11.
    Fishman GA, Jampol LM, Goldberg MF (1976) Diagnostic features of the Favre-Goldmann syndrome. Br J Ophthalmol 60(5):345–353CrossRefGoogle Scholar
  12. 12.
    Jacobson SG, Román AJ, Román MI, Gass JD, Parker JA (1991) Relatively enhanced S cone function in the Goldmann-Favre syndrome. Am J Ophthalmol 111(4):446–453CrossRefGoogle Scholar
  13. 13.
    Bonilha VL, Fishman GA, Rayborn ME, Hollyfield JG (2009) Retinal pathology of a patient with Goldmann-Favre syndrome. Ophthalmic Genet 30(4):172–180CrossRefGoogle Scholar
  14. 14.
    Pachydaki SI, Bhatnagar PA, Barbazetto IA, Klaver CC, Freund BK, Yannuzzi LA (2009) Long-term follow-up in enhanced s-cone syndrome. Retin Cases Brief Rep 3(2):118–120CrossRefGoogle Scholar
  15. 15.
    Kuniyoshi K, Hayashi T, Sakuramoto H, Nakao A, Sato T, Utsumi T, Tsuneoka H, Shimomura Y (2013) Novel mutations in enhanced S-cone syndrome. Ophthalmology 120(2):431.e1–431.e6CrossRefGoogle Scholar
  16. 16.
    Marmor MF, Jacobson SG, Foerster MH, Kellner U, Weleber RG (1990) Diagnostic clinical findings of a new syndrome with night blindness, maculopathy, and enhanced S cone sensitivity. Am J Ophthalmol 110(2):124–134CrossRefGoogle Scholar
  17. 17.
    Audo I, Michaelides M, Robson AG, Hawlina M, Vaclavik V, Sandbach JM, Neveu MM, Hogg CR, Hunt DM, Moore AT, Bird AC, Webster AR, Holder GE (2008) Phenotypic variation in enhanced S-cone syndrome. Invest Ophthalmol Vis Sci 49(5):2082–2093CrossRefGoogle Scholar
  18. 18.
    Kuniyoshi K, Hayashi T, Sakuramoto H, Mishima H, Tsuneoka H, Tsunoda K, Iwata T, Shimomura Y (2016) New truncation mutation of the NR2E3 gene in a Japanese patient with enhanced S-cone syndrome. Jpn J Ophthalmol 60(6):476–485CrossRefGoogle Scholar
  19. 19.
    Pichi F, Morara M, Veronese C, Nucci P, Ciardella AP (2013) Multimodal imaging in hereditary retinal diseases. J Ophthalmol.
  20. 20.
    Hull S, Arno G, Sergouniotis PI, Tiffin P, Borman AD, Chandra A, Robson AG, Holder GE, Webster AR, Moore AT (2014) Clinical and molecular characterization of enhanced S-cone syndrome in children. JAMA Ophthalmol 132(11):1341–1349CrossRefGoogle Scholar
  21. 21.
    Özateş S, Tekin K, Teke MY (2018) Goldmann-Favre syndrome: case series. Turk J Ophthalmol 48(1):47–51CrossRefGoogle Scholar
  22. 22.
    Ganesh A, Stroh E, Manayath GJ, Al-Zuhaibi S, Levin AV (2011) Macular cysts in retinal dystrophy. Curr Opin Ophthalmol 22(5):332–339CrossRefGoogle Scholar
  23. 23.
    Sustar M, Perovšek D, Cima I, Stirn-Kranjc B, Hawlina M, Brecelj J (2015) Electroretinography and optical coherence tomography reveal abnormal post-photoreceptoral activity and altered retinal lamination in patients with enhanced S-cone syndrome. Doc Ophthalmol 130(3):165–177CrossRefGoogle Scholar
  24. 24.
    Park SP, Hong IH, Tsang SH, Lee W, Horowitz J, Yzer S, Allikmets R, Chang S (2013) Disruption of the human cone photoreceptor mosaic from a defect in NR2E3 transcription factor function in young adults. Graefes Arch Clin Exp Ophthalmol 251(10):2299–2309CrossRefGoogle Scholar
  25. 25.
    Yzer S, Barbazetto I, Allikmets R, van Schooneveld MJ, Bergen A, Tsang SH, Jacobson SG, Yannuzzi LA (2013) Expanded clinical spectrum of enhanced S-cone syndrome. JAMA Ophthalmol 131(10):1324–1330CrossRefGoogle Scholar
  26. 26.
    Kanda A, Swaroop A (2009) A comprehensive analysis of sequence variants and putative diseasecausing mutations in photoreceptor-specific nuclear receptor NR2E3. Mol Vis 15:2174–2184Google Scholar
  27. 27.
    Roduit R, Escher P, Schorderet DF (2009) Mutations in the DNA-binding domain of NR2E3 affect in vivo dimerization and interaction with CRX. PLoS One 4(10):e7379CrossRefGoogle Scholar
  28. 28.
    Wright AF, Reddick AC, Schwartz SB, Ferguson JS, Aleman TS, Kellner U, Jurklies B, Schuster A, Zrenner E, Wissinger B, Lennon A, Shu X, Cideciyan AV, Stone EM, Jacobson SG, Swaroop A (2004) Mutation analysis of NR2E3 and NRL genes in Enhanced S Cone Syndrome. Hum Mutat 24(5):439Google Scholar
  29. 29.
    Haider NB, Jacobson SG, Cideciyan AV, Swiderski R, Streb LM, Searby C, Beck G, Hockey R, Hanna DB, Gorman S, Duhl D, Carmi R, Bennett J, Weleber RG, Fishman GA, Wright AF, Stone EM, Sheffield VC (2000) Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate. Nat Genet 24(2):127–131Google Scholar
  30. 30.
    Escher P, Gouras P, Roduit R, Tiab L, Bolay S, Delarive T, Chen S, Tsai CC, Hayashi M, Zernant J, Merriam JE, Mermod N, Allikmets R, Munier FL, Schorderet DF (2009) Mutations in NR2E3 can cause dominant or recessive retinal degenerations in the same family. Hum Mutat 30(3):342–351Google Scholar
  31. 31.
    Bocquet B, Marzouka NA, Hebrard M, Manes G, Sénéchal A, Meunier I, Hamel CP (2013) Homozygosity mapping in autosomal recessive retinitis pigmentosa families detects novel mutations. Mol Vis 19:2487–2500Google Scholar
  32. 32.
    Bessant DA, Holder GE, Fitzke FW, Payne AM, Bhattacharya SS, Bird AC (2003) Phenotype of retinitis pigmentosa associated with the Ser50Thr mutation in the NRL gene. Arch Ophthalmol 121(6):793–802CrossRefGoogle Scholar
  33. 33.
    Sohn EH, Chen FK, Rubin GS, Moore AT, Webster AR, MacLaren RE (2010) Macular function assessed by microperimetry in patients with enhanced S-cone syndrome. Ophthalmology 117(6):1199–1206.e1CrossRefGoogle Scholar
  34. 34.
    Wang NK, Fine HF, Chang S, Chou CL, Cella W, Tosi J, Lin CS, Nagasaki T, Tsang SH (2009) Cellular origin of fundus autofluorescence in patients and mice with a defective NR2E3 gene. Br J Ophthalmol 93(9):1234–1240CrossRefGoogle Scholar
  35. 35.
    Sambricio J, Tejada-Palacios P, Barceló-Mendiguchía A (2016) Choroidal neovascularization, outer retinal tubulation and fundus autofluorescence findings in a patient with enhanced S-cone syndrome. Clin Exp Ophthalmol 44(1):69–71CrossRefGoogle Scholar
  36. 36.
    Khan AO, Aldahmesh M, Meyer B (2007) The enhanced S-cone syndrome in children. Br J Ophthalmol 91(3):394–396CrossRefGoogle Scholar
  37. 37.
    Wang NK, Lai CC, Liu CH, Yeh LK, Chou CL, Kong J, Nagasaki T, Tsang SH, Chien CL (2013) Origin of fundus hyperautofluorescent spots and their role in retinal degeneration in a mouse model of Goldmann-Favre syndrome. Dis Model Mech 6(5):1113–1122CrossRefGoogle Scholar
  38. 38.
    Barteselli G (2014) Fundus autofluorescence and optical coherence tomography findings in pigmented paravenous retinochoroidal atrophy. Can J Ophthalmol 49(6):e144–e146CrossRefGoogle Scholar
  39. 39.
    Hashimoto Y, Kase S, Saito W, Ishida S (2012) Abnormalities of fundus autofluorescence in pigmented paravenous chorioretinal atrophy. Open Ophthalmol J 6:125–128CrossRefGoogle Scholar
  40. 40.
    McKay GJ, Clarke S, Davis JA, Simpson DA, Silvestri G (2005) Pigmented paravenous chorioretinal atrophy is associated with a mutation within the crumbs homolog 1 (CRB1) gene. Invest Ophthalmol Vis Sci 46(1):322–328CrossRefGoogle Scholar
  41. 41.
    Shona OA, Islam F, Robson AG, Webster AR, Moore AT, Michaelides M (2018) Pigmented PARAVENOUS CHORIORETINAL atrophy-detailed clinical study of a large cohort. RetinaGoogle Scholar
  42. 42.
    Ratra D, Chandrasekharan DP, Aruldas P, Ratra V (2016) Concurrent retinitis pigmentosa and pigmented paravenous retinochoroidal atrophy phenotypes in the same patient. Indian J Ophthalmol 64(10):775–777CrossRefGoogle Scholar
  43. 43.
    Aoki S, Inoue T, Kusakabe M, Fukushima M, Kitamoto K, Ogawa A, Yamamoto M, Obata R (2017) Unilateral pigmented paravenous retinochoroidal atrophy with retinitis pigmentosa in the contralateral eye: a case report. Am J Ophthalmol Case Rep 8:14–17CrossRefGoogle Scholar
  44. 44.
    Nakamura M, Hotta Y, Piao CH, Kondo M, Terasaki H, Miyake Y (2002) Enhanced S-cone syndrome with subfoveal neovascularization. Am J Ophthalmol 133:575–577CrossRefGoogle Scholar
  45. 45.
    Zerbib J, Blanco Garavito R, Gerber S, Oubraham H, Sikorav A, Audo I, Kaplan J, Rozet JM, Souied EH (2017) RETINOCHOROIDAL ANASTOMOSIS ASSOCIATED WITH ENHANCED S-CONE SYNDROME. Retin Cases Brief RepGoogle Scholar
  46. 46.
    Cassiman C, Spileers W, De Baere E, de Ravel T, Casteels I (2013) Peculiar fundus abnormalities and pathognomonic electrophysiological findings in a 14-month-old boy with NR2E3 mutations. Ophthalmic Genet 34(1–2):105–108CrossRefGoogle Scholar
  47. 47.
    Lam BL, Goldberg JL, Hartley KL, Stone EM, Liu M (2007) Atypical mild enhanced S-cone syndrome with novel compound heterozygosity of the NR2E3 gene. Am J Ophthalmol 144(1):157–159CrossRefGoogle Scholar
  48. 48.
    Manayath GJ, Namburi P, Periasamy S, Kale JA, Narendran V, Ganesh A (2014) A novel mutation in the NR2E3 gene associated with Goldmann-Favre syndrome and vasoproliferative tumor of the retina. Mol Vis 20:724–731Google Scholar
  49. 49.
    Thomas MG, Kumar A, Mohammad S, Proudlock FA, Engle EC, Andrews C, Chan WM, Thomas S, Gottlob I (2011) Structural grading of foveal hypoplasia using spectral-domain optical coherence tomography a predictor of visual acuity? Ophthalmology 118(8):1653–1660CrossRefGoogle Scholar
  50. 50.
    Dubis AM, Costakos DM, Subramaniam CD, Godara P, Wirostko WJ, Carroll J, Provis JM (2012) Evaluation of normal human foveal development using optical coherence tomography and histologic examination. Arch Ophthalmol 130(10):1291–1300CrossRefGoogle Scholar
  51. 51.
    Kearns TP, Hollenhorst RW (1966) Chloroquine retinopathy: evaluation by fluorescein fundus angiography. Trans Am Ophthalmol Soc 64:217–231Google Scholar
  52. 52.
    Kurz-Levin MM, Halfyard AS, Bunce C, Bird AC, Holder GE (2002) Clinical variations in assessment of bull's-eye maculopathy. Arch Ophthalmol 120(5):567–575CrossRefGoogle Scholar
  53. 53.
    Campo RV, Aaberg TM (1982) Ocular and systemic manifestations of the Bardet-Biedl syndrome. Am J Ophthalmol 94(6):750–756CrossRefGoogle Scholar
  54. 54.
    Koenekoop RK, Loyer M, Hand CK, Al Mahdi H, Dembinska O, Beneish R, Racine J, Rouleau GA (2003) Novel RPGR mutations with distinct retinitis pigmentosa phenotypes in French-Canadian families. Am J Ophthalmol 136(4):678–687CrossRefGoogle Scholar
  55. 55.
    Suzuki R, Hirose T (1998) Bull’s-eye macular dystrophy associated with peripheral involvement. Ophthalmologica 212(4):260–267CrossRefGoogle Scholar
  56. 56.
    Michaelides M, Chen LL, Brantley MA Jr, Andorf JL, Isaak EM, Jenkins SA, Holder GE, Bird AC, Stone EM, Webster AR (2007) ABCA4 mutations and discordant ABCA4 alleles in patients and siblings with bull’s-eye maculopathy. Br J Ophthalmol 91(12):1650–1655CrossRefGoogle Scholar
  57. 57.
    Michaelides M, Gaillard MC, Escher P, Tiab L, Bedell M, Borruat FX, Barthelmes D, Carmona R, Zhang K, White E, McClements M, Robson AG, Holder GE, Bradshaw K, Hunt DM, Webster AR, Moore AT, Schorderet DF, Munier FL (2010) The PROM1 mutation p.R373C causes an autosomal dominant bull’s eye maculopathy associated with rod, rod-cone, and macular dystrophy. Invest Ophthalmol Vis Sci 51(9):4771–4780CrossRefGoogle Scholar
  58. 58.
    Yang Z, Chen Y, Lillo C, Chien J, Yu Z, Michaelides M, Klein M, Howes KA, Li Y, Kaminoh Y, Chen H, Zhao C, Chen Y, Al-Sheikh YT, Karan G, Corbeil D, Escher P, Kamaya S, Li C, Johnson S, Frederick JM, Zhao Y, Wang C, Cameron DJ, Huttner WB, Schorderet DF, Munier FL, Moore AT, Birch DG, Baehr W, Hunt DM, Williams DS, Zhang K (2008) Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice. J Clin Invest 118(8):2908–2916Google Scholar
  59. 59.
    Khan KN, Robson A, OAR M, Arno G, Inglehearn CF, Armengol M, Waseem N, Holder GE, Carss KJ, Raymond LF, Webster AR, Moore AT, McKibbin M, van Genderen MM, Poulter JA, Michaelides M, UK Inherited Retinal Disease Consortium (2018) A clinical and molecular characterisation of CRB1-associated maculopathy. Eur J Hum Genet 26(5):687–694CrossRefGoogle Scholar
  60. 60.
    Hull S, Arno G, Plagnol V, Chamney S, Russell-Eggitt I, Thompson D, Ramsden SC, Black GC, Robson A, Holder GE, Moore AT, Webster AR (2014) The phenotypic variability of retinal dystrophies associated with mutations in CRX, with report of a novel macular dystrophy phenotype. Invest Ophthalmol Vis Sci 55(10):6934–6944CrossRefGoogle Scholar
  61. 61.
    Griffith JF, DeBenedictis MJ, Traboulsi EI (2018) A novel dominant CRX mutation causes adult-onset macular dystrophy. Ophthalmic Genet 39(1):120–124CrossRefGoogle Scholar
  62. 62.
    Hennig AK, Peng GH, Chen S (2008) Regulation of photoreceptor gene expression by Crx-associated transcription factor network. Brain Res 1192:114–133 ReviewCrossRefGoogle Scholar
  63. 63.
    Blanco-Kelly F, García Hoyos M, Lopez Martinez MA, Lopez-Molina MI, Riveiro-Alvarez R, Fernandez-San Jose P, Avila-Fernandez A, Corton M, Millan JM, García Sandoval B, Ayuso C (2016) Dominant retinitis pigmentosa, p.Gly56Arg mutation in NR2E3: phenotype in a large cohort of 24 cases. PLoS One 11(2):e0149473CrossRefGoogle Scholar
  64. 64.
    Greferath U, Guymer RH, Vessey KA, Brassington K, Fletcher EL (2016) Correlation of histologic features with in vivo imaging of reticular pseudodrusen. Ophthalmology 123(6):1320–1331CrossRefGoogle Scholar
  65. 65.
    Spaide RF, Ooto S, Curcio CA (2018) Subretinal drusenoid deposits AKA pseudodrusen. Surv Ophthalmol pii: S0039-6257(17)30266–7Google Scholar
  66. 66.
    Gliem M, Müller PL, Mangold E, Bolz HJ, Stöhr H, Weber BH, Holz FG, Charbel Issa P (2015) Reticular pseudodrusen in Sorsby fundus dystrophy. Ophthalmology 122(8):1555–1562CrossRefGoogle Scholar
  67. 67.
    Gliem M, Hendig D, Finger RP, Holz FG, Charbel Issa P (2015) Reticular pseudodrusen associated with a diseased bruch membrane in pseudoxanthoma elasticum. JAMA Ophthalmol 133(5):581–588 Erratum in: JAMA Ophthalmol. 2015 May;133(5):621CrossRefGoogle Scholar
  68. 68.
    Zweifel SA, Imamura Y, Freund KB, Spaide RF (2011) Multimodal fundus imaging of pseudoxanthoma elasticum. Retina 31(3):482–491CrossRefGoogle Scholar
  69. 69.
    Murro V, Mucciolo DP, Sodi A, Vannozzi L, De Libero C, Simonini G, Rizzo S (2017) Retinal capillaritis in a CRB1-associated retinal dystrophy. Ophthalmic Genet 38(6):555–558CrossRefGoogle Scholar
  70. 70.
    Aleman TS, Garrity ST, Brucker AJ (2013) Retinal structure in vitamin A deficiency as explored with multimodal imaging. Doc Ophthalmol 127(3):239–243CrossRefGoogle Scholar
  71. 71.
    Genead MA, Fishman GA, McAnany JJ (2010) Efficacy of topical dorzolamide for treatment of cystic macular lesions in a patient with enhanced S-cone syndrome. Doc Ophthalmol 121(3):231–240CrossRefGoogle Scholar
  72. 72.
    Salvatore S, Fishman GA, Genead MA (2013) Treatment of cystic macular lesions in hereditary retinal dystrophies. Surv Ophthalmol 58(6):560–584CrossRefGoogle Scholar
  73. 73.
    Lingao MD, Ganesh A, Karthikeyan AS, Al Zuhaibi S, Al-Hosni A, Al Khayat A, Capasso J, Trumler AA, Stroh E, Al Shekaili H, Cater JR, Levin AV (2016) Macular cystoid spaces in patients with retinal dystrophy. Ophthalmic Genet 37(4):377–383CrossRefGoogle Scholar
  74. 74.
    Iannaccone A, Fung KH, Eyestone ME, Stone EM (2009) Treatment of adult-onset acute macular retinoschisis in enhanced s-cone syndrome with oral acetazolamide. Am J Ophthalmol 147(2):307–312.e2CrossRefGoogle Scholar
  75. 75.
    Mahajan D, Votruba M (2017) A novel NR2E3 gene mutation in autosomal recessive retinitis pigmentosa with cystic maculopathy. Acta Ophthalmol.
  76. 76.
    Hayashi T, Gekka T, Tsuneoka H (2016) Spontaneous resolution of large macular retinoschisis in enhanced S-cone syndrome. Ophthalmic Surg Lasers Imaging Retina 47(2):187–190CrossRefGoogle Scholar
  77. 77.
    Escher P, Vaclavik V, Munier FL, Tran HV (2016) Presence of a triple concentric autofluorescence ring in NR2E3-p.G56R-linked autosomal dominant retinitis pigmentosa (ADRP). Invest Ophthalmol Vis Sci 57(4):2001–2002CrossRefGoogle Scholar

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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Surgery and Translational MedicineUniversity of FlorenceFlorenceItaly
  2. 2.Department of Genetic DiagnosisCareggi Teaching HospitalFlorenceItaly

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