{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:19:12Z","timestamp":1790849952559,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T00:00:00Z","timestamp":1707782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Van Sloun Foundation and NEI\/NIH","award":["EY-006855"],"award-info":[{"award-number":["EY-006855"]}]},{"name":"Van Sloun Foundation and NEI\/NIH","award":["#RC-CMM-0720-0792-UPA"],"award-info":[{"award-number":["#RC-CMM-0720-0792-UPA"]}]},{"name":"Foundation Fighting Blindness","award":["EY-006855"],"award-info":[{"award-number":["EY-006855"]}]},{"name":"Foundation Fighting Blindness","award":["#RC-CMM-0720-0792-UPA"],"award-info":[{"award-number":["#RC-CMM-0720-0792-UPA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>While the manifestations of many inherited retinal disorders are limited to loss of vision, others are part of a syndrome that affects multiple tissues, particularly the nervous system. Most syndromic retinal disorders are thought to be recessively inherited. Two dogs out of a litter of Cirneco dell\u2032 Etna dogs, both males, showed signs of retinal degeneration, along with tremors and signs described as either atypical seizures or paroxysmal dyskinesias, while the other two male littermates were normal. We named this oculo-neurological syndrome CONS (Cirneco oculo-neurological syndrome), and undertook homozygosity mapping and whole-genome sequencing to determine its potential genetic etiology. Notably, we detected a 1-bp deletion in chromosome 6 that was predicted to cause a frameshift and premature stop codon within the canine AMPD2 gene, which encodes adenosine monophosphate deaminase, an enzyme that converts adenosine 5\u2032-monophosphate (AMP) to inosine 5\u2019-monophosphate (IMP). Genotyping of the available Cirneco population suggested perfect segregation between cases and controls for the variant. Moreover, this variant was absent in canine genomic databases comprised of thousands of unaffected dogs. The AMPD2 genetic variant we identified in dogs presents with retinal manifestations, adding to the spectrum of neurological manifestations associated with AMPD2 variants in humans.<\/jats:p>","DOI":"10.3390\/genes15020238","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T04:18:22Z","timestamp":1707884302000},"page":"238","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Frameshift Variant in AMPD2 in Cirneco dell\u2019Etna Dogs with Retinopathy and Tremors"],"prefix":"10.3390","volume":"15","author":[{"given":"Leonardo","family":"Murgiano","sequence":"first","affiliation":[{"name":"Division of Experimental Retinal Therapies, Department of Clinical Sciences & Advanced Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Sylvia M. Van Sloun Laboratory for Canine Genomic Analysis, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica K.","family":"Niggel","sequence":"additional","affiliation":[{"name":"Division of Experimental Retinal Therapies, Department of Clinical Sciences & Advanced Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Sylvia M. Van Sloun Laboratory for Canine Genomic Analysis, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leontine","family":"Benedicenti","sequence":"additional","affiliation":[{"name":"Matthew J. Ryan Veterinary Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5161-0648","authenticated-orcid":false,"given":"Matteo","family":"Cortellari","sequence":"additional","affiliation":[{"name":"Department of Agricultural and Environmental Sciences\u2014Production, Territory, Agroenergy, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9116-3208","authenticated-orcid":false,"given":"Arianna","family":"Bionda","sequence":"additional","affiliation":[{"name":"Department of Agricultural and Environmental Sciences\u2014Production, Territory, Agroenergy, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6526-2162","authenticated-orcid":false,"given":"Paola","family":"Crepaldi","sequence":"additional","affiliation":[{"name":"Department of Agricultural and Environmental Sciences\u2014Production, Territory, Agroenergy, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3242-1817","authenticated-orcid":false,"given":"Luigi","family":"Liotta","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4028-3100","authenticated-orcid":false,"given":"Geoffrey K.","family":"Aguirre","sequence":"additional","affiliation":[{"name":"Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Beltran","sequence":"additional","affiliation":[{"name":"Division of Experimental Retinal Therapies, Department of Clinical Sciences & Advanced Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo D.","family":"Aguirre","sequence":"additional","affiliation":[{"name":"Division of Experimental Retinal Therapies, Department of Clinical Sciences & Advanced Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Sylvia M. Van Sloun Laboratory for Canine Genomic Analysis, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tatour, Y., and Ben-Yosef, T. (2020). Syndromic Inherited Retinal Diseases: Genetic, Clinical and Diagnostic Aspects. Diagnostics, 10.","DOI":"10.3390\/diagnostics10100779"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.preteyeres.2018.03.005","article-title":"Non-syndromic retinitis pigmentosa","volume":"66","author":"Verbakel","year":"2018","journal-title":"Prog. Retin. 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