Biallelic Mutations in CRB1 Underlie Autosomal Recessive Familial Foveal Retinoschisis

doi:10.1167/iovs.15-18281

. 2016 May 1;57(6):2637-46.

doi: 10.1167/iovs.15-18281.

Biallelic Mutations in CRB1 Underlie Autosomal Recessive Familial Foveal Retinoschisis

Ajoy Vincent¹, Judith Ng², Christina Gerth-Kahlert³, Erika Tavares², Jason T Maynes⁴, Thomas Wright⁵, Amit Tiwari⁶, Anupreet Tumber⁵, Shuning Li², James V M Hanson³, Angela Bahr⁶, Heather MacDonald⁷, Luzy Bähr⁶, Carol Westall⁸, Wolfgang Berger⁹, Frans P M Cremers¹⁰, Anneke I den Hollander¹¹, Elise Héon¹

Affiliations

¹ Program of Genetics and Genome Biology The Hospital for Sick Children, Toronto, Canada 2Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Canada 3Department of Ophthalmology and Vision Science.
² Program of Genetics and Genome Biology The Hospital for Sick Children, Toronto, Canada.
³ Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland.
⁴ Department of Anesthesia and Pain Medicine, and Program in Molecular Structure and Function, The Hospital for Sick Children, Toronto, Canada.
⁵ Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
⁶ Institute of Medical Molecular Genetics, University of Zürich, Wagistrasse 12, Schlieren, Switzerland.
⁷ Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Canada 7Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada 8Division of Clinical and Metabolic Genetics, The Ho.
⁸ Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Canada 3Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Canada.
⁹ Institute of Medical Molecular Genetics, University of Zürich, Wagistrasse 12, Schlieren, Switzerland 9Zurich Center for Integrative Human Physiology (ZIHP), University of Zürich, Zürich, Switzerland 10Neuroscience Center Zurich (ZNZ), University and ETH.
¹⁰ Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
¹¹ Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands 12Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, The Netherlands.

PMID: 27258436
DOI: 10.1167/iovs.15-18281

Free article

Biallelic Mutations in CRB1 Underlie Autosomal Recessive Familial Foveal Retinoschisis

Ajoy Vincent et al. Invest Ophthalmol Vis Sci. 2016.

Free article

. 2016 May 1;57(6):2637-46.

doi: 10.1167/iovs.15-18281.

Authors

Affiliations

¹ Program of Genetics and Genome Biology The Hospital for Sick Children, Toronto, Canada 2Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Canada 3Department of Ophthalmology and Vision Science.
² Program of Genetics and Genome Biology The Hospital for Sick Children, Toronto, Canada.
³ Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland.
⁴ Department of Anesthesia and Pain Medicine, and Program in Molecular Structure and Function, The Hospital for Sick Children, Toronto, Canada.
⁵ Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
⁶ Institute of Medical Molecular Genetics, University of Zürich, Wagistrasse 12, Schlieren, Switzerland.
⁷ Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Canada 7Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada 8Division of Clinical and Metabolic Genetics, The Ho.
⁸ Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Canada 3Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Canada.
⁹ Institute of Medical Molecular Genetics, University of Zürich, Wagistrasse 12, Schlieren, Switzerland 9Zurich Center for Integrative Human Physiology (ZIHP), University of Zürich, Zürich, Switzerland 10Neuroscience Center Zurich (ZNZ), University and ETH.
¹⁰ Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
¹¹ Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands 12Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, The Netherlands.

PMID: 27258436
DOI: 10.1167/iovs.15-18281

Abstract

Purpose: To identify the genetic cause of autosomal recessive familial foveal retinoschisis (FFR).

Methods: A female sibship with FFR was identified (Family-A; 17 and 16 years, respectively); panel based genetic sequencing (132 genes) and comparative genome hybridization (142 genes) were performed. Whole-exome sequencing (WES) was performed on both siblings using the Illumina-HiSeq-2500 platform. A sporadic male (Family-B; 35 years) with FFR underwent WES using Illumina NextSeq500. All three affected subjects underwent detailed ophthalmologic evaluation including fundus photography, autofluorescence imaging, spectral-domain optical coherence tomography (SD-OCT), and full-field electroretinogram (ERG).

Results: Panel-based genetic testing identified two presumed disease causing variants in CRB1 (p.Gly123Cys and p.Cys948Tyr) in Family-A sibship; no deletion or duplication was detected. WES analysis in the sibship identified nine genes with two or more shared nonsynonymous rare coding sequence variants; CRB1 remained a strong candidate gene, and CRB1 variants segregated with the disease. WES in Family-B identified two presumed disease causing variants in CRB1 (p.Ile167_Gly169del and p.Arg764Cys) that segregated with the disease phenotype. Distance visual acuity was 20/40 or better in all three affected except for the left eye of the older subject (Family-B), which showed macular atrophy. Fundus evaluation showed spoke-wheel appearance at the macula in five eyes. The SD-OCT showed macular schitic changes in inner and outer nuclear layers in all cases. The ERG responses were normal in all subjects.

Conclusions: This is the first report to implicate CRB1 as the underlying cause of FFR. This phenotype forms the mildest end of the spectrum of CRB1-related diseases.

PubMed Disclaimer

Cited by

In Silico CRISPR-Cas-Mediated Base Editing Strategies for Early-Onset, Severe Cone-Rod Retinal Degeneration in Three Crumbs homolog 1 Patients, including the Novel Variant c.2833G>A.
Shamsnajafabadi H, Kaukonen M, Bellingrath JS, MacLaren RE, Cehajic-Kapetanovic J. Shamsnajafabadi H, et al. Genes (Basel). 2024 May 15;15(5):625. doi: 10.3390/genes15050625. Genes (Basel). 2024. PMID: 38790254 Free PMC article.
Case report: Familial foveal retinoschisis caused by CRB1 gene mutation in a family with recessive inheritance.
Liu S, Ren Y, Wang D, Xiao D, Li Z, Xu D, Sun Y, Wang Z, Pang J. Liu S, et al. Front Med (Lausanne). 2023 Aug 11;10:1220075. doi: 10.3389/fmed.2023.1220075. eCollection 2023. Front Med (Lausanne). 2023. PMID: 37636578 Free PMC article.
A novel nonsense variant (c.1499C>G) in CRB1 caused Leber congenital amaurosis-8 in a Chinese family and a literature review.
Duan W, Zhou T, Jiang H, Zhang M, Hu M, Zhang L. Duan W, et al. BMC Med Genomics. 2022 Sep 17;15(1):197. doi: 10.1186/s12920-022-01356-z. BMC Med Genomics. 2022. PMID: 36115989 Free PMC article. Review.
CRB1-Associated Retinal Dystrophies: Genetics, Clinical Characteristics, and Natural History.
Daich Varela M, Georgiou M, Alswaiti Y, Kabbani J, Fujinami K, Fujinami-Yokokawa Y, Khoda S, Mahroo OA, Robson AG, Webster AR, AlTalbishi A, Michaelides M. Daich Varela M, et al. Am J Ophthalmol. 2023 Feb;246:107-121. doi: 10.1016/j.ajo.2022.09.002. Epub 2022 Sep 12. Am J Ophthalmol. 2023. PMID: 36099972 Free PMC article.
Consanguinity-based analysis of exome sequencing yields likely genetic causes in patients with inherited retinal dystrophy.
Shen RJ, Wang JG, Li Y, Jin ZB. Shen RJ, et al. Orphanet J Rare Dis. 2021 Jun 15;16(1):278. doi: 10.1186/s13023-021-01902-5. Orphanet J Rare Dis. 2021. PMID: 34130719 Free PMC article.

See all "Cited by" articles

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions

Supplementary concepts

Actions

LinkOut - more resources

Full Text Sources
- Silverchair Information Systems
- Zurich Open Access Repository and Archive
Other Literature Sources
- scite Smart Citations

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Biallelic Mutations in CRB1 Underlie Autosomal Recessive Familial Foveal Retinoschisis

Affiliations

Biallelic Mutations in CRB1 Underlie Autosomal Recessive Familial Foveal Retinoschisis

Authors

Affiliations

Abstract

Similar articles

Cited by

Publication types

MeSH terms

Substances

Supplementary concepts

LinkOut - more resources

Full Text Sources

Other Literature Sources

Abstract

Similar articles

Cited by

Publication types

MeSH terms

Substances

Supplementary concepts

Related information

LinkOut - more resources

Full Text Sources

Other Literature Sources