Variants in CFAP410 cause a range of retinal and skeletal phenotypes.

IF 4.7 2区医学 Q1 GENETICS & HEREDITY

NPJ Genomic Medicine Pub Date : 2025-04-17 DOI:10.1038/s41525-025-00489-1

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

{"title":"Variants in CFAP410 cause a range of retinal and skeletal phenotypes.","authors":"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","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"32"},"PeriodicalIF":4.7000,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006490/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"NPJ Genomic Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41525-025-00489-1","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

CFAP410的变异导致一系列视网膜和骨骼表型。

纤毛病与一系列表型相关，包括视网膜变性和骨骼异常。我们对来自世界各地多个眼科中心的49例纤毛和鞭毛相关蛋白410 （CFAP410）变异患者进行了回顾性研究。常见的临床特征包括早发性视力下降、畏光和光暗适应延迟。锥体-杆状营养不良的发生率大约是杆状-锥体营养不良的两倍。少数患者（22.4%）表现为骨骼异常，与轴向椎体干骺端发育不良（SMDAX）一致。具有最严重眼科和骨骼表型的患者在CFAP410保守的富含亮氨酸的区域内存在疾病相关变异，这些变异的结构效应使用ChimeraX建模。该报告进一步加深了我们对cfap410相关临床表型的理解，如视网膜营养不良和骨骼发育不良。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

NPJ Genomic Medicine Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.40

自引率

1.90%

发文量

审稿时长

17 weeks

期刊介绍： npj Genomic Medicine is an international, peer-reviewed journal dedicated to publishing the most important scientific advances in all aspects of genomics and its application in the practice of medicine. The journal defines genomic medicine as "diagnosis, prognosis, prevention and/or treatment of disease and disorders of the mind and body, using approaches informed or enabled by knowledge of the genome and the molecules it encodes." Relevant and high-impact papers that encompass studies of individuals, families, or populations are considered for publication. An emphasis will include coupling detailed phenotype and genome sequencing information, both enabled by new technologies and informatics, to delineate the underlying aetiology of disease. Clinical recommendations and/or guidelines of how that data should be used in the clinical management of those patients in the study, and others, are also encouraged.