CEP162 deficiency causes human retinal degeneration and reveals a dual role in ciliogenesis and neurogenesis
- Author
- Nafisa Nuzhat, Kristof Van Schil, Sandra Liakopoulos, Miriam Bauwens (UGent) , Alfredo Dueñas Rey (UGent) , Stephan Kaeseberg, Melanie Jaeger, Jason R. Willer, Jennifer Winter, Hanh M. Truong, Núria Roura Gruartmoner, Mattias Van Heetvelde (UGent) , Joachim Wolf, Robert Merget, Sabine Grasshoff-Derr, Jo Van Dorpe (UGent) , Anne Hoorens (UGent) , Heidi Stoehr, Luke Mansard, Anne-Francoise Roux, Thomas Langmann, Katharina Dannhausen, David Rosenkranz, Karl M. Wissing, Michel Van Lint, Heidi Rossmann, Friederike Haeuser, Peter Nuernberg, Holger Thiele, Ulrich Zechner, Jillian N. Pearring, Elfride De Baere (UGent) and Hanno J. Bolz
- Organization
- Project
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- Precision medicine in inherited blindness using integrated omics in human and animal models
- StarT (European Training Network to Diagnose: Understand and Treat Stargardt Disease, a Frequent Inherited Blinding Disorder - StarT)
- 3G0G3119
- 3L000709
- Unraveling the role of retinal cis-regulatory elements of the USH2A gene, located in an ultraconserved genomic regulatory block
- Abstract
- Defects in primary or motile cilia result in a variety of human pathologies, and retinal degeneration is frequently associated with these so-called ciliopathies. We found that homozygosity for a truncating variant in CEP162, a centrosome and microtubule-associated protein required for transition zone assembly during ciliogenesis and neuronal differentiation in the retina, caused late-onset retinitis pigmentosa in 2 unrelated families. The mutant CEP162-E646R*5 protein was expressed and properly localized to the mitotic spindle, but it was missing from the basal body in primary and photoreceptor cilia. This impaired recruitment of transition zone components to the basal body and corresponded to complete loss of CEP162 function at the ciliary compartment, reflected by delayed formation of dysmorphic cilia. In contrast, shRNA knockdown of Cep162 in the developing mouse retina increased cell death, which was rescued by expression of CEP162-E646R*5, indicating that the mutant retains its role for retinal neurogenesis. Human retinal degeneration thus resulted from specific loss of the ciliary function of CEP162.
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01H9JT720QB2EXJCZVW1NJDDEP
- MLA
- Nuzhat, Nafisa, et al. “CEP162 Deficiency Causes Human Retinal Degeneration and Reveals a Dual Role in Ciliogenesis and Neurogenesis.” JOURNAL OF CLINICAL INVESTIGATION, vol. 133, no. 8, 2023, doi:10.1172/JCI161156.
- APA
- Nuzhat, N., Van Schil, K., Liakopoulos, S., Bauwens, M., Dueñas Rey, A., Kaeseberg, S., … Bolz, H. J. (2023). CEP162 deficiency causes human retinal degeneration and reveals a dual role in ciliogenesis and neurogenesis. JOURNAL OF CLINICAL INVESTIGATION, 133(8). https://doi.org/10.1172/JCI161156
- Chicago author-date
- Nuzhat, Nafisa, Kristof Van Schil, Sandra Liakopoulos, Miriam Bauwens, Alfredo Dueñas Rey, Stephan Kaeseberg, Melanie Jaeger, et al. 2023. “CEP162 Deficiency Causes Human Retinal Degeneration and Reveals a Dual Role in Ciliogenesis and Neurogenesis.” JOURNAL OF CLINICAL INVESTIGATION 133 (8). https://doi.org/10.1172/JCI161156.
- Chicago author-date (all authors)
- Nuzhat, Nafisa, Kristof Van Schil, Sandra Liakopoulos, Miriam Bauwens, Alfredo Dueñas Rey, Stephan Kaeseberg, Melanie Jaeger, Jason R. Willer, Jennifer Winter, Hanh M. Truong, Núria Roura Gruartmoner, Mattias Van Heetvelde, Joachim Wolf, Robert Merget, Sabine Grasshoff-Derr, Jo Van Dorpe, Anne Hoorens, Heidi Stoehr, Luke Mansard, Anne-Francoise Roux, Thomas Langmann, Katharina Dannhausen, David Rosenkranz, Karl M. Wissing, Michel Van Lint, Heidi Rossmann, Friederike Haeuser, Peter Nuernberg, Holger Thiele, Ulrich Zechner, Jillian N. Pearring, Elfride De Baere, and Hanno J. Bolz. 2023. “CEP162 Deficiency Causes Human Retinal Degeneration and Reveals a Dual Role in Ciliogenesis and Neurogenesis.” JOURNAL OF CLINICAL INVESTIGATION 133 (8). doi:10.1172/JCI161156.
- Vancouver
- 1.Nuzhat N, Van Schil K, Liakopoulos S, Bauwens M, Dueñas Rey A, Kaeseberg S, et al. CEP162 deficiency causes human retinal degeneration and reveals a dual role in ciliogenesis and neurogenesis. JOURNAL OF CLINICAL INVESTIGATION. 2023;133(8).
- IEEE
- [1]N. Nuzhat et al., “CEP162 deficiency causes human retinal degeneration and reveals a dual role in ciliogenesis and neurogenesis,” JOURNAL OF CLINICAL INVESTIGATION, vol. 133, no. 8, 2023.
@article{01H9JT720QB2EXJCZVW1NJDDEP,
abstract = {{Defects in primary or motile cilia result in a variety of human pathologies, and retinal degeneration is frequently associated with these so-called ciliopathies. We found that homozygosity for a truncating variant in CEP162, a centrosome and microtubule-associated protein required for transition zone assembly during ciliogenesis and neuronal differentiation in the retina, caused late-onset retinitis pigmentosa in 2 unrelated families. The mutant CEP162-E646R*5 protein was expressed and properly localized to the mitotic spindle, but it was missing from the basal body in primary and photoreceptor cilia. This impaired recruitment of transition zone components to the basal body and corresponded to complete loss of CEP162 function at the ciliary compartment, reflected by delayed formation of dysmorphic cilia. In contrast, shRNA knockdown of Cep162 in the developing mouse retina increased cell death, which was rescued by expression of CEP162-E646R*5, indicating that the mutant retains its role for retinal neurogenesis. Human retinal degeneration thus resulted from specific loss of the ciliary function of CEP162.}},
articleno = {{e161156}},
author = {{Nuzhat, Nafisa and Van Schil, Kristof and Liakopoulos, Sandra and Bauwens, Miriam and Dueñas Rey, Alfredo and Kaeseberg, Stephan and Jaeger, Melanie and Willer, Jason R. and Winter, Jennifer and Truong, Hanh M. and Roura Gruartmoner, Núria and Van Heetvelde, Mattias and Wolf, Joachim and Merget, Robert and Grasshoff-Derr, Sabine and Van Dorpe, Jo and Hoorens, Anne and Stoehr, Heidi and Mansard, Luke and Roux, Anne-Francoise and Langmann, Thomas and Dannhausen, Katharina and Rosenkranz, David and Wissing, Karl M. and Van Lint, Michel and Rossmann, Heidi and Haeuser, Friederike and Nuernberg, Peter and Thiele, Holger and Zechner, Ulrich and Pearring, Jillian N. and De Baere, Elfride and Bolz, Hanno J.}},
issn = {{0021-9738}},
journal = {{JOURNAL OF CLINICAL INVESTIGATION}},
language = {{eng}},
number = {{8}},
pages = {{14}},
title = {{CEP162 deficiency causes human retinal degeneration and reveals a dual role in ciliogenesis and neurogenesis}},
url = {{http://doi.org/10.1172/JCI161156}},
volume = {{133}},
year = {{2023}},
}
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