{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:32:13Z","timestamp":1790947933508,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,5]],"date-time":"2023-03-05T00:00:00Z","timestamp":1677974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Veterinary Ophthalmology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To describe the clinical, preliminary electroretinographic and optical coherence tomography features of a newly identified form of progressive retinal atrophy (PRA) in German Spitzes, and identify the causal gene mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Animals<\/jats:title><jats:p>Thirty\u2010three client\u2010owned German Spitz dogs were included.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedures<\/jats:title><jats:p>All animals underwent a full ophthalmic examination, including vision testing. In addition, fundus photography, ERG, and OCT were performed. A DNA\u2010marker\u2010based association analysis was performed to screen potential candidate genes and the whole genomes of four animals were sequenced.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Initial fundus changes were pale papilla and mild vascular attenuation. Oscillatory nystagmus was noted in 14 of 16 clinically affected puppies. Vision was impaired under both scotopic and photopic conditions. Rod\u2010mediated ERGs were unrecordable in all affected dogs tested, reduced cone\u2010mediated responses were present in one animal at 3\u00a0months of age and unrecordable in the other affected animals tested. Multiple small retinal bullae were observed in three clinically affected animals (two with confirmed genetic diagnosis). OCT showed that despite loss of function, retinal structure was initially well\u2010preserved, although a slight retinal thinning developed in older animals with the ventral retina being more severely affected. Pedigree analysis supported an autosomal recessive inheritance. A mutation was identified in GUCY2D, which segregated with the disease (NM_001003207.1:c.1598_1599insT; p.(Ser534GlufsTer20)). Human subjects with GUCY2D mutations typically show an initial disconnect between loss of function and loss of structure, a feature recapitulated in the affected dogs in this study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We identified early\u2010onset PRA in the German Spitz associated with a frameshift mutation in GUCY2D.<\/jats:p><\/jats:sec>","DOI":"10.1111\/vop.13079","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T05:46:28Z","timestamp":1678081588000},"page":"532-547","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Preliminary characterization of a novel form of progressive retinal atrophy in the German Spitz dog associated with a frameshift mutation in <i>GUCY2D<\/i>"],"prefix":"10.1111","volume":"26","author":[{"given":"Mariza","family":"Bortolini","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine Federal University of Paran\u00e1  Curitiba Puerto Rico Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige A.","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Small Animal Clinical Sciences, College of Veterinary Medicine Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos Duque","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine Federal University of Paran\u00e1  Curitiba Puerto Rico Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario Teruo","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Federal University of Paran\u00e1  Curitiba Paran\u00e1 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca Luiza Valduga","family":"Guareschi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine Federal University of Paran\u00e1  Curitiba Puerto Rico Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7410-2304","authenticated-orcid":false,"given":"Simon M.","family":"Petersen\u2010Jones","sequence":"additional","affiliation":[{"name":"Department of Small Animal Clinical Sciences, College of Veterinary Medicine Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3933-8864","authenticated-orcid":false,"given":"Fabiano","family":"Montiani\u2010Ferreira","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine Federal University of Paran\u00e1  Curitiba Puerto Rico Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-019-01999-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9040882"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.10.1169"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.visres.2009.04.008"},{"key":"e_1_2_7_6_1","first-page":"5","article-title":"A review of research to elucidate the causes of the generalized progressive retinal atrophies","volume":"155","author":"Petersen\u2010Jones SM","year":"1998","journal-title":"J vet Med"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-011-9361-3"},{"key":"e_1_2_7_8_1","first-page":"126","article-title":"Genetic screening for PRA\u2010associated mutations in multiple dog breeds shows that PRA is heterogeneous within and between breeds","volume":"7","author":"Downs LM","year":"2013","journal-title":"Vet Ophthalmol"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01203343"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2052.2012.02379.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1999.5754"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/vop.12284"},{"key":"e_1_2_7_13_1","first-page":"1637","article-title":"cGMP phosphodiesterase\u2010 mutation causes progressive retinal atrophy in the Cardigan welsh corgi dog","volume":"40","author":"Petersen\u2013Jones SM","year":"1999","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000056785"},{"key":"e_1_2_7_15_1","first-page":"195","article-title":"Utility of colored\u2010light pupil response in patients with age\u2010related macular degeneration","volume":"44","author":"Asakawa K","year":"2014","journal-title":"Kitasato Arch Exp Med"},{"key":"e_1_2_7_16_1","first-page":"14","article-title":"Genomic deletion of CNGB3 is identical by descent in multiple canine breeds and causes achromatopsia","volume":"20","author":"Yeh CY","year":"2013","journal-title":"BMC Genomics"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021452"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106610"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1089\/humc.2014.155"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/jhered\/esg015"},{"key":"e_1_2_7_21_1","first-page":"193","article-title":"Progressive retinal atrophy in the Abyssinian cat: clinical characteristics","volume":"26","author":"Narfstr\u00f6m K","year":"1985","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1463-5224.1999.00049.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/685901"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/vop.12448"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0137072"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2004.04.003"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.277"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/vop.12315"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/age.13118"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsap.13120"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.2005.66.1798"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/vop.12683"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/vop.12792"},{"key":"e_1_2_7_34_1","first-page":"119","article-title":"Clinical studies on progressive retinal atrophy in 31 dogs","volume":"18","author":"Kelawala DN","year":"2017","journal-title":"Iran J Vet Res"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-17121-0_34"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2019.10.019"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2021.108637"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/vop.12932"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2016-309975"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12081261"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.12685"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oret.2022.03.008"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.10.003"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200503"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-14-05889.1999"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030201"}],"container-title":["Veterinary Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/vop.13079","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/vop.13079","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/vop.13079","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T10:00:30Z","timestamp":1702029630000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/vop.13079"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,5]]},"references-count":45,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1111\/vop.13079"],"URL":"https:\/\/doi.org\/10.1111\/vop.13079","archive":["Portico"],"relation":{},"ISSN":["1463-5216","1463-5224"],"issn-type":[{"value":"1463-5216","type":"print"},{"value":"1463-5224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,5]]},"assertion":[{"value":"2022-06-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}