{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:06:39Z","timestamp":1791583599667,"version":"4.3.4"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":2955,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["OD 010939"],"award-info":[{"award-number":["OD 010939"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>GM2-gangliosidosis is a fatal neurodegenerative lysosomal storage disease (LSD) caused by deficiency of either \u03b2-hexosaminidase A (Hex-A) and \u03b2-hexosaminidase B (Hex-B) together, or the GM2 activator protein. Clinical signs can be variable and are not pathognomonic for the specific, causal deficiency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To characterize the phenotype and genotype of GM2-gangliosidosis disease in an affected dog.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>One affected Shiba Inu and a clinically healthy dog.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical and neurologic evaluation, brain magnetic resonance imaging (MRI), assays of lysosomal enzyme activities, and sequencing of all coding regions of HEXA, HEXB, and GM2A genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A 14-month-old, female Shiba Inu presented with clinical signs resembling GM2-gangliosidosis in humans and GM1-gangliosidosis in the Shiba Inu. Magnetic resonance imaging (MRI) of the dog's brain indicated neurodegenerative disease, and evaluation of cerebrospinal fluid (CSF) identified storage granules in leukocytes. Lysosomal enzyme assays of plasma and leukocytes showed deficiencies of Hex-A and Hex-B activities in both tissues. Genetic analysis identified a homozygous, 3-base pair deletion in the HEXB gene (c.618-620delCCT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Clinical Importance<\/jats:title>\n                    <jats:p>Clinical, biochemical, and molecular features are characterized in a Shiba Inu with GM2-gangliosidosis. The deletion of 3 adjacent base pairs in HEXB predicts the loss of a leucine residue at amino acid position 207 (p.Leu207del) supporting the hypothesis that GM2-gangliosidosis seen in this dog is the Sandhoff type. Because GM1-gangliosidosis also exists in this breed with almost identical clinical signs, genetic testing for both GM1- and GM2-gangliosidosis should be considered to make a definitive diagnosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.14862","type":"journal-article","created":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T09:12:37Z","timestamp":1509959557000},"page":"340-347","source":"Crossref","is-referenced-by-count":8,"title":["Canine GM2-Gangliosidosis Sandhoff Disease Associated with a 3-Base Pair Deletion in the\n                    <i>HEXB G<\/i>\n                    ene"],"prefix":"10.1093","volume":"32","author":[{"given":"P.","family":"Wang","sequence":"first","affiliation":[{"name":"Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.S.","family":"Henthorn","sequence":"additional","affiliation":[{"name":"Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Galban","sequence":"additional","affiliation":[{"name":"Section of Neurology & Neurosurgery, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Lin","sequence":"additional","affiliation":[{"name":"Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Takedai","sequence":"additional","affiliation":[{"name":"Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1224-6708","authenticated-orcid":false,"given":"M.","family":"Casal","sequence":"additional","affiliation":[{"name":"Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,1,1]]},"reference":[{"key":"2026020303250061400_jvim14862-bib-0001","first-page":"3827","article-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Gravel","year":"2001","edition":"8"},{"key":"2026020303250061400_jvim14862-bib-0002","first-page":"3827","article-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Suzuki","year":"2001","edition":"8"},{"key":"2026020303250061400_jvim14862-bib-0003","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1023\/A:1021280007739","article-title":"A novel mutation in the gene for canine acid beta-galactosidase that causes GM1-gangliosidosis in Shiba dogs","volume":"25","author":"Yamato","year":"2002","journal-title":"J Inherit Metab Dis"},{"key":"2026020303250061400_jvim14862-bib-0004","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1292\/jvms.65.213","article-title":"Clinical and clinico-pathologic characteristics of Shiba dogs with a deficiency of lysosomal acid beta-galactosidase: A canine model of human GM1 gangliosidosis","volume":"65","author":"Yamato","year":"2003","journal-title":"J Vet Med Sci"},{"key":"2026020303250061400_jvim14862-bib-0005","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1136\/vr.146.17.493","article-title":"GM1 gangliosidosis in Shiba dogs","volume":"146","author":"Yamato","year":"2000","journal-title":"Vet Rec"},{"key":"2026020303250061400_jvim14862-bib-0006","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/1746-6148-9-132","article-title":"Molecular epidemiology of canine GM1 gangliosidosis in the Shiba Inu breed in Japan: Relationship between regional prevalence and carrier frequency","volume":"9","author":"Uddin","year":"2013","journal-title":"BMC Vet Res"},{"key":"2026020303250061400_jvim14862-bib-0007","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/BF00687364","article-title":"Morphological and neurochemical investigations of 2 types of amaurotic idiocy in the dog. 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