Coding and non-coding variants in the ciliopathy gene CFAP410 cause early-onset non-syndromic retinal degeneration
Inherited retinal degenerations are blinding genetic disorders characterized by high genetic and phenotypic heterogeneity. In this retrospective study, we describe sixteen families with early-onset non-syndromic retinal degenerations in which affected probands carried rare bi-allelic variants in CFAP410, a ciliary gene previously associated with recessive Jeune syndrome. We detected twelve variants, eight of which were novel, including c.373+91A>G, which led to aberrant splicing. To our knowledge this is the first likely pathogenic deep-intronic variant identified in this gene. Analysis of all reported and novel CFAP410 variants revealed no clear correlation between the severity of the CFAP410-associated phenotypes and the identified causal variants. This is supported by the fact that the frequently encountered missense variant p.(Arg73Pro), often found in syndromic cases, was also associated with non-syndromic retinal degeneration. This study expands the current knowledge of CFAP410-associated ciliopathy by enriching its mutational landscape and supports its association with non-syndromic retinal degeneration.
Authors
- Kinga M. Bujakowska (ORCID: https://orcid.org/0000-0001-6809-9818)
- Riccardo Sangermano (ORCID: https://orcid.org/0000-0001-8657-0810)
- Stephanie DiTroia (ORCID: https://orcid.org/0000-0002-6847-6780)
- Isabelle S. Audo (ORCID: https://orcid.org/0000-0003-0698-5309)
- Xavier Zanlonghi (ORCID: https://orcid.org/0000-0003-4460-5346)
- Rachel M. Huckfeldt (ORCID: https://orcid.org/0000-0002-9220-2261)
- José-Alain Sahel
- Eric A. Pierce (ORCID: https://orcid.org/0000-0002-2354-4102)
- Shizuo Mukai (ORCID: https://orcid.org/0000-0002-0330-0127)
- Priya Gupta (ORCID: https://orcid.org/0000-0002-9296-5904)
- Christina Zeitz (ORCID: https://orcid.org/0000-0002-3510-1712)
- Jinu Han (ORCID: https://orcid.org/0000-0002-8607-6625)
- Christel Condroyer (ORCID: https://orcid.org/0009-0000-6189-0906)
- Jacque L. Duncan (ORCID: https://orcid.org/0000-0002-9593-6412)
- Emily Place (ORCID: https://orcid.org/0000-0002-1748-5644)
- Emily O’Heir (ORCID: https://orcid.org/0000-0001-7669-8239)
- C W Price
- Aline Antonio (ORCID: https://orcid.org/0000-0001-5942-9555)
- Julien Navarro (ORCID: https://orcid.org/0009-0000-0448-5461)
Institutions
- Broad Institute (US)
- Massachusetts Eye and Ear Infirmary (US)
- Centre National de la Recherche Scientifique (FR)
- Institut de la Vision (FR)
- Harvard University (US)
- Inserm (FR)
- University of California, San Francisco (US)
- Yonsei University (KR)
- Centre hospitalier national d'ophtalmologie des Quinze-Vingts (FR)
- Sorbonne Université (FR)
- University of Pittsburgh Medical Center (US)
- Gangnam Severance Hospital (KR)
- Centre Hospitalier Universitaire de Rennes (FR)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- npj Genomic Medicine
- Published
- 2024-11-08
- DOI
- https://doi.org/10.1038/s41525-024-00439-3
- Citations
- 2
- Primary Topic
- RNA regulation and disease
- Type
- article
- Field-Weighted Citation Impact
- 0.47
Funders
- Broad Institute
- Foundation Fighting Blindness
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Radboud Universiteit
- Centre National de la Recherche Scientifique
- Radboud Universitair Medisch Centrum
- University of California, San Diego
- National Human Genome Research Institute
- National Eye Institute