{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T07:03:07Z","timestamp":1774422187194,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T00:00:00Z","timestamp":1636934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["grant number 310030_200354"],"award-info":[{"award-number":["grant number 310030_200354"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Ichthyoses are hereditary skin disorders characterized by the formation of scales and defects in the outermost layer of the epidermis. In dogs, at least six different breed-specific ichthyoses including a relatively common PNPLA1-related autosomal recessive ichthyosis in Golden Retrievers are known. In this study, we investigated 14 Golden Retrievers with scales that were not homozygous for the mutant PNPLA1 allele suggesting a genetically distinct new form of ichthyosis. Histopathological examinations showed lamellar, orthokeratotic hyperkeratosis, and mildly hyperplastic epidermis that led to the diagnosis of a nonepidermolytic ichthyosis. Combined linkage and homozygosity mapping in 14 cases and 30 nonaffected family members delimited a critical interval of \u223c12.7\u2009Mb on chromosome 23. Whole-genome sequencing of an affected dog revealed a single protein-changing variant within this region that was not present in 795 control genomes. The identified variant is a 14\u2009bp deletion in the ABHD5 gene (c.1006_1019del), leading to a frameshift and altering the last 14 codons p.(Asp336Serfs*6). The genotypes at this variant showed perfect cosegregation with the ichthyosis phenotype in a large family comprising 14 cases and 72 controls. ABHD5 encodes an acyltransferase required for lipid metabolism. In humans, variants in ABHD5 cause Chanarin-Dorfman syndrome, a neutral lipid storage disease with ichthyosis. Our data in dogs together with the knowledge on the effects of ABHD5 variants in humans strongly suggest ABHD5:c.1006_1019del as candidate causative genetic variant for a new canine form of ichthyosis, which we propose to designate as Golden Retriever ichthyosis type 2 (ICH2).<\/jats:p>","DOI":"10.1093\/g3journal\/jkab397","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T04:05:43Z","timestamp":1637208343000},"source":"Crossref","is-referenced-by-count":12,"title":["<i>ABHD5<\/i> frameshift deletion in Golden Retrievers with ichthyosis"],"prefix":"10.1093","volume":"12","author":[{"given":"Sarah","family":"Kiener","sequence":"first","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"},{"name":"Dermfocus, University of Bern, Bern 3001, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique J","family":"Wiener","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, Texas A&M University, College of Veterinary Medicine and Biomedical Sciences, College Station, TX 77843-4467, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaitlin","family":"Hopke","sequence":"additional","affiliation":[{"name":"Department of Small Animal Clinical Sciences, Texas A&M University, College of Veterinary Medicine and Biomedical Sciences, College Station, TX 77843-4474, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison B","family":"Diesel","sequence":"additional","affiliation":[{"name":"Department of Small Animal Clinical Sciences, Texas A&M University, College of Veterinary Medicine and Biomedical Sciences, College Station, TX 77843-4474, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vidhya","family":"Jagannathan","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A","family":"Mauldin","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margret L","family":"Casal","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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"},{"name":"Dermfocus, University of Bern, Bern 3001, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,11,15]]},"reference":[{"key":"2022022805092086200_jkab397-B1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/ng786","article-title":"Merlin\u2014rapid analysis of dense genetic maps using sparse gene flow trees","volume":"30","author":"Abecasis","year":"2002","journal-title":"Nat Genet"},{"key":"2022022805092086200_jkab397-B2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.ejmg.2012.01.013","article-title":"Novel nonsense mutation of ABHD5 in Dorfman-Chanarin syndrome with unusual findings: a challenge for genotype-phenotype correlation","volume":"55","author":"Aggarwal","year":"2012","journal-title":"Eur J Med Genet"},{"key":"2022022805092086200_jkab397-B3","doi-asserted-by":"crossref","first-page":"e1006651","DOI":"10.1371\/journal.pgen.1006651","article-title":"A de novo variant in the ASPRV1 gene in a dog with 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Bulldogs","volume":"12","author":"Casal","year":"2017","journal-title":"PLoS One"},{"key":"2022022805092086200_jkab397-B7","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1136\/bmj.1.5957.553","article-title":"Neutral-lipid storage disease: a new disorder of lipid metabolism","volume":"1","author":"Chanarin","year":"1975","journal-title":"Br Med J"},{"key":"2022022805092086200_jkab397-B8","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","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly (Austin)"},{"key":"2022022805092086200_jkab397-B9","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/j.1365-2133.2005.06735.x","article-title":"Mild recessive epidermolytic hyperkeratosis associated with a novel keratin 10 donor splice-site mutation in a family of Norfolk terrier 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