Skip to main content

Advertisement

SpringerLink
Log in

A novel tandem duplication of PRDM13 in a Chinese family with North Carolina macular dystrophy

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

A Letter to the Editor (by invitation) to this article was published on 16 February 2023

Abstract

Purposes

North Carolina macular dystrophy (NCMD) is a rare autosomal dominant inherited disorder characterized by macular impairment with a variety of phenotypic manifestations. The aims of this study were to assess the clinical features of a Chinese family with NCMD and to identify the underlying genetic cause of the disease.

Methods

Three patients from a Chinese family were included in this study. Detailed ophthalmological examinations were performed, including best corrected visual acuity (BCVA), slit lamp, dilated indirect ophthalmoscopy, fundus photography, optical coherence tomography (OCT), fundus autofluorescence, full-field electroretinography (ERG), and electrooculography (EOG). Genomic DNA was extracted from peripheral blood samples. Whole-genome sequencing and long-read genome sequencing were applied to detect the pathogenic variants. Sanger sequencing was performed to confirm the breakpoints.

Results

All three patients had macular involvement ranging from patchy yellowish-white lesions to big-area thinning, which are typical for NCMD. The BCVA ranged from 20/50 to 20/20. OCT revealed varying degrees of macular structure disorganization. The ERG responses were normal, and the Arden ration of the EOG was reduced. A novel 134.6 kb (g.99932464-100067110dup) tandem duplication on chromosome 6 (NC_000006.11) encompassing the entire CCNC and PRDM13 genes and a DNase 1 hypersensitivity site in the MCDR1 locus was identified.

Conclusion

A novel large tandem duplication in MCDR1 locus was confirmed in a Chinese family with NCMD with a variety of macular phenotypes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Lefler WH, Wadsworth JA, Sidbury JB Jr (1971) Hereditary macular degeneration and amino-aciduria. Am J Ophthalmol 71:224–230

    Article  CAS  PubMed  Google Scholar 

  2. Small KW (1989) North Carolina macular dystrophy, revisited. Ophthalmology 96:1747–1754. https://doi.org/10.1016/s0161-6420(89)32655-8

    Article  CAS  PubMed  Google Scholar 

  3. Kiernan DF, Shah RJ, Hariprasad SM, Grassi MA, Small KW, Kiernan JP, Mieler WF (2011) Thirty-Year follow-up of an African American family with macular dystrophy of the retina, locus 1 (North Carolina macular dystrophy). Ophthalmology 118:1435–1443. https://doi.org/10.1016/j.ophtha.2010.10.041

    Article  PubMed  Google Scholar 

  4. Reichel MB, Kelsell RE, Fan J, Gregory CY, Evans K, Moore AT, Hunt DM, Fitzke FW, Bird AC (1998) Phenotype of a British North Carolina macular dystrophy family linked to chromosome 6q. Br J Ophthalmol 82:1162–1168. https://doi.org/10.1136/bjo.82.10.1162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Small KW, Weber JL, Roses A, Lennon F, Vance JM, Pericak-Vance MA (1992) North Carolina macular dystrophy is assigned to chromosome 6. Genomics 13:681–685. https://doi.org/10.1016/0888-7543(92)90141-e

    Article  CAS  PubMed  Google Scholar 

  6. Small KW, Puech B, Mullen L, Yelchits S (1997) North Carolina macular dystrophy phenotype in France maps to the MCDR1 locus. Mol Vis 3:1

    CAS  PubMed  Google Scholar 

  7. Michaelides M, Johnson S, Tekriwal AK, Holder GE, Bellmann C, Kinning E, Woodruff G, Trembath RC, Hunt DM, Moore AT (2003) An early-onset autosomal dominant macular dystrophy (MCDR3) resembling north carolina macular dystrophy maps to chromosome 5. Invest Opthalmol Vis Sci 44:2178. https://doi.org/10.1167/iovs.02-1094

    Article  Google Scholar 

  8. Rosenberg T, Roos B, Johnsen T, Bech N, Scheetz TE, Larsen M, Stone EM, Fingert JH (2010) Clinical and genetic characterization of a Danish family with North Carolina macular dystrophy. Mol Vis 16:2659–2668

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Small KW, DeLuca AP, Whitmore SS, Rosenberg T, Silva-Garcia R, Udar N, Puech B, Garcia CA, Rice TA, Fishman GA, Héon E, Folk JC, Streb LM, Haas CM, Wiley LA, Scheetz TE, Fingert JH, Mullins RF, Tucker BA, Stone EM (2016) North Carolina macular dystrophy is caused by dysregulation of the retinal transcription factor PRDM13. Ophthalmology 123:9–18. https://doi.org/10.1016/j.ophtha.2015.10.006

    Article  PubMed  Google Scholar 

  10. Bowne SJ, Sullivan LS, Wheaton DK, Locke KG, Jones KD, Koboldt DC, Fulton RS, Wilson RK, Blanton SH, Birch DG, Daiger SP (2016) North Carolina macular dystrophy (MCDR1) caused by a novel tandem duplication of the PRDM13 gene. Mol Vis 22:1239–1247

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Manes G, Joly W, Guignard T, Smirnov V, Berthemy S, Bocquet B, Audo I, Zeitz C, Sahel J, Cazevieille C, Sénéchal A, Deleuze JF, Blanché-Koch H, Boland A, Carroll P, Geneviève D, Zanlonghi X, Arndt C, Hamel CP, Defoort-Dhellemmes S, Meunier I (2017) A novel duplication of PRMD13 causes North Carolina macular dystrophy: overexpression of PRDM13 orthologue in drosophila eye reproduces the human phenotype. Hum Mol Genet 26:4367–4374. https://doi.org/10.1093/hmg/ddx322

    Article  CAS  PubMed  Google Scholar 

  12. Tandon M, Barnett C, Taranath D (2019) Case report: North Carolina macular dystrophy misdiagnosed as congenital ocular toxoplasmosis. Mol Vis 25:731–733

    PubMed  PubMed Central  Google Scholar 

  13. Ellingford JM, Sergouniotis PI, Jenkins E, Black GC (2017) Genome sequencing identifies a non-coding variant in the MCDR1 locus as a cause of macular dystrophy. Clin Experiment Ophthalmol 45:297–299. https://doi.org/10.1111/ceo.12825

    Article  PubMed  Google Scholar 

  14. Small KW, Tran EM, Small L, Rao RC, Shaya F (2019) Multimodal imaging and functional testing in a North Carolina macular disease family: toxoplasmosis, fovea plana, and torpedo maculopathy are phenocopies. Ophthalmology Retina 3:607–614. https://doi.org/10.1016/j.oret.2019.03.002

    Article  PubMed  Google Scholar 

  15. Bakall B, Bryan JS 3rd, Stone EM, Small KW (2018) Choroidal neovascularization in north carolina macular dystrophy responsive to anti-vascular endothelial growth factor therapy. Retin Cases Brief Rep. https://doi.org/10.1097/icb.0000000000000838

    Article  Google Scholar 

  16. Birtel J, Gliem M, Herrmann P, Neuhaus C, Holz FG, MacLaren RE, Scholl HPN, Charbel Issa P (2021) North Carolina macular dystrophy shows a particular drusen phenotype and atrophy progression. Br J Ophthalmol. https://doi.org/10.1136/bjophthalmol-2021-318815

    Article  PubMed  Google Scholar 

  17. Small KW, DeLuca AP, Whitmore SS, Rosenberg T, Silva-Garcia R, Udar N, Puech B, Garcia CA, Rice TA, Fishman GA, Heon E, Folk JC, Streb LM, Haas CM, Wiley LA, Scheetz TE, Fingert JH, Mullins RF, Tucker BA, Stone EM (2016) North Carolina macular dystrophy is caused by dysregulation of the retinal transcription factor PRDM13. Ophthalmology 123:9–18. https://doi.org/10.1016/j.ophtha.2015.10.006

    Article  PubMed  Google Scholar 

  18. Cipriani V, Silva RS, Arno G, Pontikos N, Kalhoro A, Valeina S, Inashkina I, Audere M, Rutka K, Puech B, Michaelides M, van Heyningen V, Lace B, Webster AR, Moore AT (2017) Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus. Sci Rep 7:7512. https://doi.org/10.1038/s41598-017-06387-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Small KW, Garcia CA, Gallardo G, Udar N, Yelchits S (1998) North Carolina macular dystrophy (MCDR1) in Texas. Retina (Philadelphia, Pa) 18:448–452

    CAS  PubMed  Google Scholar 

  20. Rabb MF, Mullen L, Yelchits S, Udar N, Small KW (1998) A North Carolina macular dystrophy phenotype in a Belizean family maps to the MCDR1 locus. Am J Ophthalmol 125:502–508. https://doi.org/10.1016/s0002-9394(99)80191-3

    Article  CAS  PubMed  Google Scholar 

  21. Pauleikhoff D, Sauer CG, Müller CR, Radermacher M, Merz A, Weber BH (1997) Clinical and genetic evidence for autosomal dominant North Carolina macular dystrophy in a German family. Am J Ophthalmol 124:412–415. https://doi.org/10.1016/s0002-9394(14)70842-6

    Article  CAS  PubMed  Google Scholar 

  22. Kim SJ, Woo SJ, Yu HG (2006) A Korean family with an early-onset autosomal dominant macular dystrophy resembling North Carolina macular dystrophy. Korean J Ophthalmol 20:220–224. https://doi.org/10.3341/kjo.2006.20.4.220

    Article  PubMed  PubMed Central  Google Scholar 

  23. Yang Z, Tong Z, Chorich LJ, Pearson E, Yang X, Moore A, Hunt DM, Zhang K (2008) Clinical characterization and genetic mapping of North Carolina macular dystrophy. Vision Res 48:470–477. https://doi.org/10.1016/j.visres.2007.09.015

    Article  CAS  PubMed  Google Scholar 

  24. Namburi P, Khateb S, Meyer S, Bentovim T, Ratnapriya R, Khramushin A, Swaroop A, Schueler-Furman O, Banin E, Sharon D (2020) A unique PRDM13-associated variant in a Georgian Jewish family with probable North Carolina macular dystrophy and the possible contribution of a unique CFH variant. Mol Vis 26:299–310

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Small KW (1998) North Carolina macular dystrophy: clinical features, genealogy, and genetic linkage analysis. Trans Am Ophthalmol Soc 96:925–961

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Small KW, Killian J, McLean WC (1991) North Carolina’s dominant progressive foveal dystrophy: how progressive is it? Br J Ophthalmol 75:401–406. https://doi.org/10.1136/bjo.75.7.401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Francis PJ, Johnson S, Edmunds B, Kelsell RE, Sheridan E, Garrett C, Holder GE, Hunt DM, Moore AT (2003) Genetic linkage analysis of a novel syndrome comprising North Carolina-like macular dystrophy and progressive sensorineural hearing loss. Br J Ophthalmol 87:893–898. https://doi.org/10.1136/bjo.87.7.893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Rhee DY, Reichel E, Rogers A, Strominger M (2007) Subfoveal choroidal neovascularization in a 3-year-old child with North Carolina macular dystrophy. J AAPOS 11:614–615. https://doi.org/10.1016/j.jaapos.2007.06.010

    Article  PubMed  Google Scholar 

  29. Stone EM, Nichols BE, Kimura AE, Weingeist TA, Drack A, Sheffield VC (1994) Clinical features of a Stargardt-like dominant progressive macular dystrophy with genetic linkage to chromosome 6q. Arch Ophthalmol 112:765–772. https://doi.org/10.1001/archopht.1994.01090180063036

    Article  CAS  PubMed  Google Scholar 

  30. Khurana RN, Sun X, Pearson E, Yang Z, Harmon J, Goldberg MF, Zhang K (2009) A reappraisal of the clinical spectrum of North Carolina macular dystrophy. Ophthalmology 116:1976–1983. https://doi.org/10.1016/j.ophtha.2009.03.028

    Article  PubMed  Google Scholar 

  31. Boon CJ, Klevering BJ, Leroy BP, Hoyng CB, Keunen JE, den Hollander AI (2009) The spectrum of ocular phenotypes caused by mutations in the BEST1 gene. Prog Retin Eye Res 28:187–205. https://doi.org/10.1016/j.preteyeres.2009.04.002

    Article  CAS  PubMed  Google Scholar 

  32. Hartzell C, Qu Z, Putzier I, Artinian L, Chien LT, Cui Y (2005) Looking chloride channels straight in the eye: bestrophins, lipofuscinosis, and retinal degeneration. Physiology (Bethesda) 20:292–302. https://doi.org/10.1152/physiol.00021.2005

    Article  CAS  PubMed  Google Scholar 

  33. Hartzell HC, Qu Z, Yu K, Xiao Q, Chien LT (2008) Molecular physiology of bestrophins: multifunctional membrane proteins linked to best disease and other retinopathies. Physiol Rev 88:639–672. https://doi.org/10.1152/physrev.00022.2007

    Article  CAS  PubMed  Google Scholar 

  34. Xu F, Dong F, Li H, Li X, Jiang R, Sui R (2013) Phenotypic characterization of a Chinese family with autosomal dominant cone-rod dystrophy related to GUCY2D. Doc Ophthalmol 126:233–240. https://doi.org/10.1007/s10633-013-9383-0

    Article  PubMed  Google Scholar 

  35. Fog CK, Galli GG, Lund AH (2012) PRDM proteins: important players in differentiation and disease. BioEssays 34:50–60. https://doi.org/10.1002/bies.201100107

    Article  CAS  PubMed  Google Scholar 

  36. Watanabe S, Sanuki R, Sugita Y, Imai W, Yamazaki R, Kozuka T, Ohsuga M, Furukawa T (2015) Prdm13 regulates subtype specification of retinal amacrine interneurons and modulates visual sensitivity. J Neurosci 35:8004–8020. https://doi.org/10.1523/jneurosci.0089-15.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ohori S, Tsuburaya RS, Kinoshita M, Miyagi E, Mizuguchi T, Mitsuhashi S, Frith MC, Matsumoto N (2021) Long-read whole-genome sequencing identified a partial MBD5 deletion in an exome-negative patient with neurodevelopmental disorder. J Hum Genet. https://doi.org/10.1038/s10038-020-00893-8

    Article  PubMed  Google Scholar 

  38. Jiang F, Lyu GZ, Zhang VW, Li DZ (2021) Identification of thalassemia gene cluster deletion by long-read whole-genome sequencing (LR-WGS). Int J Lab Hematol. https://doi.org/10.1111/ijlh.13452

    Article  PubMed  Google Scholar 

  39. Logsdon GA, Vollger MR, Eichler EE (2020) Long-read human genome sequencing and its applications. Nat Rev Genet 21:597–614. https://doi.org/10.1038/s41576-020-0236-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Marshall CR, Bick D, Belmont JW, Taylor SL, Ashley E, Dimmock D, Jobanputra V, Kearney HM, Kulkarni S, Rehm H (2020) The Medical Genome Initiative: moving whole-genome sequencing for rare disease diagnosis to the clinic. Genome Med 12:48. https://doi.org/10.1186/s13073-020-00748-z

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank the patients for taking part in this research.

Funding

This work was supported by the National Natural Science Foundation of China (81873687).

Author information

Authors and Affiliations

  1. Department of Ophthalmology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Shijing Wu, Zhisheng Yuan, Zixi Sun, Tian Zhu, Xing Wei, Xuan Zou & Ruifang Sui

Authors
  1. Shijing Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhisheng Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zixi Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tian Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xing Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xuan Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ruifang Sui
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ruifang Sui.

Ethics declarations

Ethics approval

This study was approved by the Institutional Review Board of Peking Union Medical College Hospital.

Consent for publication

Obtained.

Conflict of interest

The authors declare no competing interests.

Disclaimer

The authors alone are responsible for the content and writing of the article.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, S., Yuan, Z., Sun, Z. et al. A novel tandem duplication of PRDM13 in a Chinese family with North Carolina macular dystrophy. Graefes Arch Clin Exp Ophthalmol 260, 645–653 (2022). https://doi.org/10.1007/s00417-021-05376-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-021-05376-w

Keywords

Search

Navigation