{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:31:32Z","timestamp":1790641892226,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Different breed-specific inherited cataracts have been described in dogs. In this study, we investigated an inbred family of Wirehaired Pointing Griffon dogs in which three offspring were affected by juvenile cataract. The pedigree suggested monogenic autosomal recessive inheritance of the trait. Whole-genome sequencing of an affected dog revealed 12 protein-changing variants that were not present in 566 control genomes, of which two were located in functional candidate genes, FYCO1 and CRYGB. Targeted genotyping of both variants in the investigated family excluded CRYGB and revealed perfect co-segregation of the FYCO1 variant with the juvenile cataract phenotype. This variant, FYCO1:c.2024delG, represents a 1 bp frameshift deletion predicted to truncate ~50% of the open reading frame p.(Ser675Thrfs*5). FYCO1 encodes the FYVE and coiled-coil domain autophagy adaptor 1, a known regulator of lens autophagy, which is required for the normal homeostasis in the eye. In humans, at least 37 pathogenic variants in FYCO1 have been shown to cause autosomal recessive cataract. Fcyo1\u2212\/\u2212 knockout mice also develop cataracts. Together with the current knowledge on FYCO1 variants and their functional impact in humans and mice, our data strongly suggest FYCO1:c.2024delG as a candidate causative variant for the observed juvenile cataract in Wirehaired Pointing Griffon dogs. To the best of our knowledge, this study represents the first report of a FYCO1-related cataract in domestic animals.<\/jats:p>","DOI":"10.3390\/genes13020334","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T03:46:00Z","timestamp":1644810360000},"page":"334","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["FYCO1 Frameshift Deletion in Wirehaired Pointing Griffon Dogs with Juvenile Cataract"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7043-3117","authenticated-orcid":false,"given":"Gabriela","family":"Rudd Garces","sequence":"first","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"},{"name":"Institute of Veterinary Genetics \u201cIng. Fernando Noel Dulout\u201d, National University of La Plata, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3275-5929","authenticated-orcid":false,"given":"Matthias","family":"Christen","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Loechel","sequence":"additional","affiliation":[{"name":"VetGen, Ann Arbor, MI 48108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8155-0041","authenticated-orcid":false,"given":"Vidhya","family":"Jagannathan","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-4880","authenticated-orcid":false,"given":"Tosso","family":"Leeb","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/S0140-6736(17)30544-5","article-title":"Cataracts","volume":"390","author":"Liu","year":"2017","journal-title":"Lancet"},{"key":"ref_2","first-page":"77","article-title":"Pediatric cataract: Challenges and future directions","volume":"9","author":"Medsinge","year":"2015","journal-title":"Clin. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000442495","article-title":"Genetics of congenital cataract","volume":"57","author":"Pichi","year":"2016","journal-title":"Dev. Ophthalmol."},{"key":"ref_4","first-page":"2007","article-title":"Cat-Map: Putting cataract on the map","volume":"16","author":"Shiels","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"107872","DOI":"10.1016\/j.exer.2019.107872","article-title":"Molecular genetics of congenital cataracts","volume":"191","author":"Li","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1136\/bjophthalmol-2019-315282","article-title":"Inherited cataracts: Molecular genetics, clinical features, disease mechanisms and novel therapeutic approaches","volume":"104","author":"Berry","year":"2020","journal-title":"Br. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev-vision-091517-034346","article-title":"Biology of inherited cataracts and opportunities for treatment","volume":"5","author":"Shiels","year":"2019","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_8","unstructured":"Maggs, D.J., Miller, P.E., and Ofri, R. (2016). Diseases of the lens. Slatter\u2019s Fundamentals of Veterinary Ophthalmology, Elsevier. [6th ed.]."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"222","DOI":"10.2460\/ajvr.69.2.222","article-title":"Inheritance of cataracts and primary lens luxation in Jack Russell Terriers","volume":"69","author":"Oberbauer","year":"2008","journal-title":"Am. J. Vet. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/vop.12167","article-title":"Prevalence and formation of primary cataracts and persistent hyperplastic tunica vasculosa lentis in the German Pinscher population in Germany","volume":"18","author":"Pfahler","year":"2015","journal-title":"Vet. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/j.1463-5224.2005.00352.x","article-title":"Prevalence of primary breed-related cataracts in the dog in North America","volume":"8","author":"Gelatt","year":"2005","journal-title":"Vet. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1046\/j.1463-5224.2003.00258.x","article-title":"Cataracts in the Bichon Frise","volume":"6","author":"Gelatt","year":"2003","journal-title":"Vet. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/j.1463-5224.2006.00460.x","article-title":"Cataract in the UK Leonberger population","volume":"9","author":"Heinrich","year":"2006","journal-title":"Vet. Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1463-5224.2006.00496.x","article-title":"Identification of mutations in HSF4 in dogs of three different breeds with hereditary cataracts","volume":"9","author":"Mellersh","year":"2006","journal-title":"Vet. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1093\/jhered\/esm043","article-title":"Mutation in HSF4 associated with early but not late-onset hereditary cataract in the Boston Terrier","volume":"98","author":"Mellersh","year":"2007","journal-title":"J. Hered."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1111\/j.1463-5224.2009.00735.x","article-title":"Mutation in HSF4 is associated with hereditary cataract in the Australian Shepherd","volume":"12","author":"Mellersh","year":"2009","journal-title":"Vet. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s00335-015-9562-2","article-title":"A novel locus on canine chromosome 13 is associated with cataract in the Australian Shepherd breed of domestic dog","volume":"26","author":"Ricketts","year":"2015","journal-title":"Mamm. Genome"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/j.1439-0388.2007.00663.x","article-title":"Evaluation of canine heat-shock transcription factor 4 as a candidate for primary cataracts in English Cocker Spaniels and wire-haired Kromfohrlanders","volume":"124","author":"Engelhardt","year":"2007","journal-title":"J. Anim. Breed. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1463-5224.2007.00598.x","article-title":"Evaluation of canine heat shock transcription factor 4 (HSF4) as a candidate gene for primary cataracts in the Dachshund and the Entlebucher Mountain dog","volume":"11","author":"Distl","year":"2008","journal-title":"Vet. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/age.12834","article-title":"A comprehensive biomedical variant catalogue based on whole genome sequences of 582 dogs and eight wolves","volume":"50","author":"Jagannathan","year":"2019","journal-title":"Anim. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nbt.1754","article-title":"Integrative genomics viewer","volume":"29","author":"Robinson","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_23","unstructured":"(2022, January 18). OMIA\u2014Online Mendelian Inheritance in Animals. Available online: https:\/\/omia.org\/."},{"key":"ref_24","unstructured":"(2022, January 18). OMIM\u2014Online mendelian Inheritance in Man. Available online: https:\/\/www.omim.org\/."},{"key":"ref_25","unstructured":"(2022, January 18). MGI\u2014Mouse Genome Informatics. Available online: http:\/\/www.informatics.jax.org\/."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1093\/bioinformatics\/btv195","article-title":"PROVEAN web server: A tool to predict the functional effect of amino acid substitutions and indels","volume":"31","author":"Choi","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5918","DOI":"10.1038\/s41467-020-19669-x","article-title":"Inferring the molecular and phenotypic impact of amino acid variants with MutPred2","volume":"11","author":"Pejaver","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bendl, J., Stourac, J., Salanda, O., Pavelka, A., Wieben, E.D., Zendulka, J., Brezovsky, J., and Damborsky, J. (2014). PredictSNP: Robust and accurate consensus classifier for prediction of disease-related mutations. PLoS Comput. Biol., 10.","DOI":"10.1371\/journal.pcbi.1003440"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/sj.ejhg.5200758","article-title":"The transcriptional map of the common eliminated region 1 (C3CER1) in 3p21.3","volume":"10","author":"Kiss","year":"2002","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_30","first-page":"1773","article-title":"Spatial expression patterns of autophagy genes in the eye lens and induction of autophagy in lens cells","volume":"18","author":"Brennan","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"550","DOI":"10.4161\/auto.6.4.11670","article-title":"FYCO1: Linking autophagosomes to microtubule plus end-directing molecular motors","volume":"6","author":"Pankiv","year":"2010","journal-title":"Autophagy"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13771","DOI":"10.1038\/s41598-021-93110-1","article-title":"Loss of FYCO1 leads to cataract formation","volume":"11","author":"Satoh","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.exer.2013.08.017","article-title":"Autophagy and mitophagy participate in ocular lens organelle degradation","volume":"116","author":"Costello","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.exer.2014.04.010","article-title":"Autophagy in the eye: Implications for ocular cell health","volume":"124","author":"Frost","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.ajhg.2011.05.008","article-title":"Mutations in FYCO1 cause autosomal-recessive congenital cataracts","volume":"88","author":"Chen","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1167\/iovs.17-21469","article-title":"Molecular genetic analysis of Pakistani families with autosomal recessive congenital cataracts by homozygosity screening","volume":"58","author":"Chen","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_37","first-page":"334","article-title":"Mutations in FYCO1 identified in families with congenital cataracts","volume":"26","author":"Iqbal","year":"2020","journal-title":"Mol. Vis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1080\/13816810.2021.1955277","article-title":"Identification of a novel nonsense variant in FYCO1 gene associated with infantile cataract and cortical atrophy","volume":"42","author":"Aprahamian","year":"2021","journal-title":"Ophthalmic Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/s41431-021-00833-w","article-title":"Autosomal recessive cataract (CTRCT18) in the Yakut population isolate of Eastern Siberia: A novel founder variant in the FYCO1 gene","volume":"29","author":"Barashkov","year":"2021","journal-title":"Eur. J. Hum. Genet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/2\/334\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:17:22Z","timestamp":1760134642000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/2\/334"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,11]]},"references-count":39,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["genes13020334"],"URL":"https:\/\/doi.org\/10.3390\/genes13020334","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,11]]}}}