Variants in CFAP410 cause a range of retinal and skeletal phenotypes

Ciliopathies are associated with a range of phenotypes including retinal degeneration and skeletal abnormalities. We present a retrospective study of 49 patients with variants in Cilia and Flagella Associated Protein 410 (CFAP410) from multiple ophthalmic centers across the world. Common clinical features included early-onset reduced visual acuity, photophobia, and delayed light-to-dark adaptation. A cone-rod dystrophy pattern was observed roughly two times more commonly than rod-cone dystrophy. A minority of patients (22.4%) presented with skeletal abnormalities consistent with axial spondylometaphyseal dysplasia (SMDAX). Patients with the most severe ophthalmic and skeletal phenotypes had disease-associated variants within conserved leucine-rich regions of CFAP410, and the structural effects of these variants were modelled using ChimeraX. This report furthers our understanding of CFAP410-associated clinical phenotypes such as retinal dystrophy and skeletal dysplasia.

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Journal
npj Genomic Medicine
Published
2025-04-17
DOI
https://doi.org/10.1038/s41525-025-00489-1
Primary Topic
Retinal Development and Disorders
Type
article
Field-Weighted Citation Impact
0.00

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article

Variants in CFAP410 cause a range of retinal and skeletal phenotypes

Amy E. Pohodich, Rebeca Azevedo Souza Amaral, Lucas Janeschitz‐Kriegl, Emily H. Jung et al.
npj Genomic Medicine
Retinal Development and Disorders
article

Variants in CFAP410 cause a range of retinal and skeletal phenotypes

Amy E. Pohodich, Rebeca Azevedo Souza Amaral, Lucas Janeschitz‐Kriegl, Emily H. Jung, Wadih M. Zein, Samuel Koller, Benjamin Bakall, Byron L. Lam, Brian P. Brooks, Catherine A. Cukras, Susanne Kohl, U. U. Graf, Andrea L. Vincent, Michael B. Gorin, Nieraj Jain, Deepika C Parameswarappa, Jordi Maggi, Christina Gerth‐Kahlert, Juliana Maria Ferraz Sallum, Sarah Hull, Mohamed M. Sylla, David G. Birch, Paul Yang, Hendrik P. N. Scholl, James V. M. Hanson, Michelle Alabek, Katarína Štingl, José‐Alain Sahel, Kaylie Webb-Jones, Alessandro Iannaccone, Omar A. Mahroo, Lesley Everett, Elias I. Traboulsi, Michalis Georgiou, Michel Michaelides, Jacque L. Duncan, Maria M. van Genderen, Milda Reith, Elise Héon, Molly Marra, Ajoy Vincent, Andrew R. Webster, Robert B. Hufnagel, Mark E. Pennesi, Reinhold E. Schmidt, Wolfgang Berger, Stephen H. Tsang, Tomas S. Aleman, Matthias Tedeus
article en

Abstract

Ciliopathies are associated with a range of phenotypes including retinal degeneration and skeletal abnormalities. We present a retrospective study of 49 patients with variants in Cilia and Flagella Associated Protein 410 (CFAP410) from multiple ophthalmic centers across the world. Common clinical features included early-onset reduced visual acuity, photophobia, and delayed light-to-dark adaptation. A cone-rod dystrophy pattern was observed roughly two times more commonly than rod-cone dystrophy. A minority of patients (22.4%) presented with skeletal abnormalities consistent with axial spondylometaphyseal dysplasia (SMDAX). Patients with the most severe ophthalmic and skeletal phenotypes had disease-associated variants within conserved leucine-rich regions of CFAP410, and the structural effects of these variants were modelled using ChimeraX. This report furthers our understanding of CFAP410-associated clinical phenotypes such as retinal dystrophy and skeletal dysplasia.

npj Genomic MedicineVol. 10(1)
University of North Carolina at Chapel Hill (US), National Institutes of Health (US), University of Arizona (US), Penn Presbyterian Medical Center (US), University of Miami (US), Emory University (US), University of Auckland (NZ), University of California, Los Angeles (US), Legacy Health (US), Oregon Health & Science University (US), University of Pittsburgh (US), Duke University (US), University of Phoenix (US), University of California, San Francisco (US), University of Basel (CH), University of Zurich (CH), Hospital for Sick Children (CA), University Medical Center Utrecht (NL), ETH Zurich (CH), California Retina Consultants (US), Greenlane Clinical Centre (NZ), Presbyterian Hospital (US), University Hospital of Zurich (CH), Schulthess-Klinik (CH), Institute of Human Genetics (PL), Swiss Integrative Center for Human Health (CH), Retina Foundation of the Southwest (US), National Eye Institute (US), New Zealand Christians in Science (NZ), The London College (GB), STZ eyetrial (DE), Moorfields Eye Hospital (GB), Bartiméus (NL), Cleveland Eye Clinic (US), Astellas Pharma (United States) (US), Institute of Molecular and Clinical Ophthalmology Basel (CH), University College London (GB), University of Pennsylvania (US), University of Tübingen (DE), Universidade Federal de São Paulo (BR)
Research to Prevent Blindness, National Institutes of Health, University of California, San Francisco, National Eye Institute, National Institute of Allergy and Infectious Diseases
Zero hunger
Openalex Percentile: Top 93%
Retinal Development and Disorders
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