{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T08:38:33Z","timestamp":1782290313460,"version":"3.54.5"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":3077,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001458","name":"AKC Canine Health Foundation","doi-asserted-by":"publisher","award":["02257"],"award-info":[{"award-number":["02257"]}],"id":[{"id":"10.13039\/100001458","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Consistent with a tentative diagnosis of neuronal ceroid lipofuscinosis (NCL), autofluorescent cytoplasmic storage bodies were found in neurons from the brains of 2 related Shiba Inu dogs with a young-adult onset, progressive neurodegenerative disease. Unexpectedly, no potentially causal NCL-related variants were identified in a whole-genome sequence generated with DNA from 1 of the affected dogs. Instead, the whole-genome sequence contained a homozygous 3 base pair (bp) deletion in a coding region of HEXB. The other affected dog also was homozygous for this 3-bp deletion. Mutations in the human HEXB ortholog cause Sandhoff disease, a type of GM2 gangliosidosis. Thin-layer chromatography confirmed that GM2 ganglioside had accumulated in an affected Shiba Inu brain. Enzymatic analysis confirmed that the GM2 gangliosidosis resulted from a deficiency in the HEXB encoded protein and not from a deficiency in products from HEXA or GM2A, which are known alternative causes of GM2 gangliosidosis. We conclude that the homozygous 3-bp deletion in HEXB is the likely cause of the Shiba Inu neurodegenerative disease and that whole-genome sequencing can lead to the early identification of potentially disease-causing DNA variants thereby refocusing subsequent diagnostic analyses toward confirming or refuting candidate variant causality.<\/jats:p>","DOI":"10.1111\/jvim.14794","type":"journal-article","created":{"date-parts":[[2017,8,21]],"date-time":"2017-08-21T00:42:39Z","timestamp":1503276159000},"page":"1520-1526","source":"Crossref","is-referenced-by-count":20,"title":["GM2 Gangliosidosis in Shiba Inu Dogs with an In-Frame Deletion in\n                    <i>HEXB<\/i>"],"prefix":"10.1093","volume":"31","author":[{"given":"A.","family":"Kolicheski","sequence":"first","affiliation":[{"name":"University of Missouri Department of Veterinary Pathobiology, , Columbia, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2225-3204","authenticated-orcid":false,"given":"G.S.","family":"Johnson","sequence":"additional","affiliation":[{"name":"University of Missouri Department of Veterinary Pathobiology, , Columbia, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.A.","family":"Villani","sequence":"additional","affiliation":[{"name":"University of Missouri Department of Veterinary Pathobiology, , Columbia, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.P.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"University of Missouri Department of Veterinary Medicine and Surgery, , Columbia, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Mhlanga-Mutangadura","sequence":"additional","affiliation":[{"name":"University of Missouri Department of Veterinary Pathobiology, , Columbia, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.A.","family":"Wenger","sequence":"additional","affiliation":[{"name":"Jefferson Medical College Department of Neurology, , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Mikoloski","sequence":"additional","affiliation":[{"name":"Pittsburgh Veterinary Specialty and Emergency Center , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.S.","family":"Eagleson","sequence":"additional","affiliation":[{"name":"Veterinary Specialty and Emergency Center, Blue Pearl Veterinary Partners , Levittown, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.F.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Division of Animal Sciences, University of Missouri , Columbia, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.D.","family":"Schnabel","sequence":"additional","affiliation":[{"name":"Division 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