Variants in CFAP410 cause a range of retinal and skeletal phenotypes

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

doi:10.1038/s41525-025-00489-1

Variants in CFAP410 cause a range of retinal and skeletal phenotypes

Ryan E Schmidt
, Amy E Pohodich
, David Birch
, Kaylie Jones
, Byron L Lam
, Emily H Jung
, Nieraj Jain
, Michalis Georgiou
, Omar A Mahroo
, Andrew R Webster
, Michel Michaelides
, Benjamin Bakall
, Alessandro Iannaccone
, Ajoy Vincent
, Deepika C Parameswarappa
, Elise Heon
, Hendrik P N Scholl
, Lucas Janeschitz-Kriegl
, Elias I Traboulsi
, Wadih Zein

Brian P Brooks, Catherine Cukras, Robert Hufnagel, Tomas S Aleman, Mohamed M Sylla, Stephen H Tsang, Michelle Alabek, Jose Sahel, Michael B Gorin, Maria M van Genderen, Katarina Stingl, Milda Reith, Susanne Kohl, Rebeca Azevedo Souza Amaral, Juliana Maria Ferraz Sallum, Andrea L Vincent, Sarah Hull, Jacque L Duncan, James V M Hanson, Matthias Tedeus, Jordi Maggi, Urs Graf, Samuel Koller, Wolfgang Berger, Christina Gerth-Kahlert, Molly Marra, Lesley A Everett, Paul Yang, Mark E Pennesi^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	32
Number of pages	11
Journal	npj Genomic Medicine
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41525-025-00489-1
Publication status	Published - 17 Apr 2025

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s41525-025-00489-1Final published version, 2.09 MBLicence: CC BY-NC-ND

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Schmidt, R. E., Pohodich, A. E., Birch, D., Jones, K., Lam, B. L., Jung, E. H., Jain, N., Georgiou, M., Mahroo, O. A., Webster, A. R., Michaelides, M., Bakall, B., Iannaccone, A., Vincent, A., Parameswarappa, D. C., Heon, E., Scholl, H. P. N., Janeschitz-Kriegl, L., Traboulsi, E. I., ... Pennesi, M. E. (2025). Variants in CFAP410 cause a range of retinal and skeletal phenotypes. npj Genomic Medicine, 10(1), Article 32. https://doi.org/10.1038/s41525-025-00489-1

@article{44a9c35063174ae8a6c5b68c85638c14,

title = "Variants in CFAP410 cause a range of retinal and skeletal phenotypes",

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.",

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

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = apr,

day = "17",

doi = "10.1038/s41525-025-00489-1",

language = "English",

volume = "10",

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Schmidt, RE, Pohodich, AE, Birch, D, Jones, K, Lam, BL, Jung, EH, Jain, N, Georgiou, M, Mahroo, OA, Webster, AR, Michaelides, M, Bakall, B, Iannaccone, A, Vincent, A, Parameswarappa, DC, Heon, E, Scholl, HPN, Janeschitz-Kriegl, L, Traboulsi, EI, Zein, W, Brooks, BP, Cukras, C, Hufnagel, R, Aleman, TS, Sylla, MM, Tsang, SH, Alabek, M, Sahel, J, Gorin, MB, van Genderen, MM, Stingl, K, Reith, M, Kohl, S, Amaral, RAS, Sallum, JMF, Vincent, AL, Hull, S, Duncan, JL, Hanson, JVM, Tedeus, M, Maggi, J, Graf, U, Koller, S, Berger, W, Gerth-Kahlert, C, Marra, M, Everett, LA, Yang, P & Pennesi, ME 2025, 'Variants in CFAP410 cause a range of retinal and skeletal phenotypes', npj Genomic Medicine, vol. 10, no. 1, 32. https://doi.org/10.1038/s41525-025-00489-1

TY - JOUR

T1 - Variants in CFAP410 cause a range of retinal and skeletal phenotypes

AU - Schmidt, Ryan E

AU - Pohodich, Amy E

AU - Birch, David

AU - Jones, Kaylie

AU - Lam, Byron L

AU - Jung, Emily H

AU - Jain, Nieraj

AU - Georgiou, Michalis

AU - Mahroo, Omar A

AU - Webster, Andrew R

AU - Michaelides, Michel

AU - Bakall, Benjamin

AU - Iannaccone, Alessandro

AU - Vincent, Ajoy

AU - Parameswarappa, Deepika C

AU - Heon, Elise

AU - Scholl, Hendrik P N

AU - Janeschitz-Kriegl, Lucas

AU - Traboulsi, Elias I

AU - Zein, Wadih

AU - Brooks, Brian P

AU - Cukras, Catherine

AU - Hufnagel, Robert

AU - Aleman, Tomas S

AU - Sylla, Mohamed M

AU - Tsang, Stephen H

AU - Alabek, Michelle

AU - Sahel, Jose

AU - Gorin, Michael B

AU - van Genderen, Maria M

AU - Stingl, Katarina

AU - Reith, Milda

AU - Kohl, Susanne

AU - Amaral, Rebeca Azevedo Souza

AU - Sallum, Juliana Maria Ferraz

AU - Vincent, Andrea L

AU - Hull, Sarah

AU - Duncan, Jacque L

AU - Hanson, James V M

AU - Tedeus, Matthias

AU - Maggi, Jordi

AU - Graf, Urs

AU - Koller, Samuel

AU - Berger, Wolfgang

AU - Gerth-Kahlert, Christina

AU - Marra, Molly

AU - Everett, Lesley A

AU - Yang, Paul

AU - Pennesi, Mark E

PY - 2025/4/17

Y1 - 2025/4/17

N2 - 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.

AB - 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.

U2 - 10.1038/s41525-025-00489-1

DO - 10.1038/s41525-025-00489-1

M3 - Article

C2 - 40246852

VL - 10

JO - npj Genomic Medicine

JF - npj Genomic Medicine

IS - 1

M1 - 32

ER -

Variants in CFAP410 cause a range of retinal and skeletal phenotypes

Abstract

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