Abstract
Introduction
We present two patients, the proband and the affected sibling, with biallelic CRB1 mutations leading to a macular dystrophy.
Case presentation
We present two patients, the proband and the affected sibling, with biallelic CRB1 mutations leading to a macular dystrophy. With 15 years of follow-up for the proband, we illustrate the natural history of CRB1 maculopathy based on clinical examination, multimodal imaging, and electrophysiology. In addition, we demonstrate the wide phenotypic spectrum of the condition with the affected sister harboring the same variants but with much milder phenotypic manifestations.
Conclusion
In addition to a previously described pathogenic variant, Ile167_Gly169del, one pathogenic missense variant in CRB1, Lys801Ter, not previously associated with macular dystrophy, is reported here. While CRB1 mutations have been more commonly described in retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), we demonstrate that mutations in CRB1 can cause a maculopathy with initial features similar to fenestrated sheen macular dystrophy (FSMD) that later evolves into severe macular atrophy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Khan KN, Robson A, Mahroo OAR et al (2018) A clinical and molecular characterisation of CRB1-associated maculopathy. Eur J Hum Genet 26(5):687–694
Talib M, Van Schooneveld MJ, Van Genderen MM et al (2017) Genotypic and phenotypic characteristics of crb1-associated retinal dystrophies: a long-term follow-up study. Ophthalmology 124(6):884–895
Lotery AJ, Jacobson SG, Fishman GF et al (2001) Mutations in the CRB1 gene cause Leber congenital amaurosis. Arch Ophthalmol 119(3):415–420
Shah N, Damani MR, Zhu XS et al (2017) Isolated maculopathy associated with biallelic CRB1 mutations. Ophthalmic Genet 38(2):190–193
Tsang SH, Burke T, Oll M et al (2014) Whole exome sequencing identifies CRB1 defect in an unusual maculopathy phenotype. Ophthalmology 121(9):1773–1782
Wolfson Y, Applegate CD, Strauss RW, Han IC, Scholl HP (2015) CRB1-related maculopathy with cystoid macular edema. JAMA Ophthalmol 133(11):1357–1360
Al Sulaiman H, Schatz P, Nowilaty SR, Abdelkader E, Abu Safieh L (2017) Diffuse retinal vascular leakage and cone-rod dystrophy in a family with the homozygous missense C.1429G>A (P.GLY477ARG) mutation in CRB1. Retin Cases Brief Rep 14(2):203–210
Hood DC, Bach M, Brigell M et al (2012) International Society For Clinical Electrophysiology of Vision (2012). ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition). Doc Ophthalmol 124:1–13
Khan SA, Nestel AR (2019) CRB1 gene mutation causing different phenotypes of Leber congenital amaurosis in siblings. J Ophthalmic Vis Res 14(4):518–524
den Hollander AI et al (2001) Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene. Am J Hum Genet 69(1):198–203
Den Hollander AI, Heckenlively JR, Van Den Born LI et al (2001) Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene. Am J Hum Genet 69(1):198–203
Sadaka A, Sisk RA (2016) Dramatic regression of macular and peripheral retinoschisis with dorzolamide 2% in X-linked retinoschisis: a case report. J Med Case Rep 10(1):142
Acknowledgements
We are thankful for the participation of the patient and her family. Kayliana J. Wesby, MS, assisted in drafting and editing the manuscript. Poulami Borkar, MBBS, assisted in editing the manuscript. This report was supported by funding from Search for Vision (Chicago, IL), National Eye Institute (Bethesda, MD) R01EY023644, departmental core grant EY001792, and Research to Prevent Blindness (New York, NY) (departmental support). The funding organizations had no role in the design or conduct of this research.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Each author warrants that he or she has no commercial associations that might pose a conflict of interest in connection with the submitted article. We hereby declare that none of the authors have a proprietary interest.
Statement of human rights
The two patients were not seen in a research context, but rather they were seen in the course of routine clinical care. Consent was obtained from the patients so as to present the findings in this manuscript. The listed funding offset administrative costs for both the department as well as the lab in addition to providing partial general salary support for one of the investigators.
Statement on the welfare of animals
There were no animals involved in this study.
Informed consent
The patient has consented to the submission of the case report for submission to the journal.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Oh, D.J., Daily, M.J. & Grassi, M.A. CRB1 maculopathy presenting as fenestrated sheen macular dystrophy with 15-year follow-up. Doc Ophthalmol 142, 381–388 (2021). https://doi.org/10.1007/s10633-020-09810-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10633-020-09810-y