{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:55:14Z","timestamp":1790358914531,"version":"4.1.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"33","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,8,17]]},"abstract":"<jats:p>\n                    Neuronal ceroid lipofuscinoses (NCLs) represent the most common group of inherited progressive encephalopathies in children. They are characterized by progressive loss of vision, mental and motor deterioration, epileptic seizures, and premature death. Rare adult forms of NCL with late onset are known as Kufs\u2019 disease. Loci underlying these adult forms remain unknown due to the small number of patients and genetic heterogeneity. Here we confirm that a late-onset form of NCL recessively segregates in US and French pedigrees of American Staffordshire Terrier (AST) dogs. Through combined association, linkage, and haplotype analyses, we mapped the disease locus to a single region of canine chromosome 9. We eventually identified a worldwide breed-specific variant in exon 2 of the\n                    <jats:italic>Arylsulfatase G<\/jats:italic>\n                    (\n                    <jats:italic>ARSG<\/jats:italic>\n                    ) gene, which causes a p.R99H substitution in the vicinity of the catalytic domain of the enzyme. In transfected cells or leukocytes from affected dogs, the missense change leads to a 75% decrease in sulfatase activity, providing a functional confirmation that the variant might be the NCL-causing mutation. Our results uncover a protein involved in neuronal homeostasis, identify a family of candidate genes to be screened in patients with Kufs' disease, and suggest that a deficiency in sulfatase is part of the NCL pathogenesis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0914206107","type":"journal-article","created":{"date-parts":[[2010,8,2]],"date-time":"2010-08-02T23:35:49Z","timestamp":1280792149000},"page":"14775-14780","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":79,"title":["A canine\n                    <i>Arylsulfatase G<\/i>\n                    (\n                    <i>ARSG<\/i>\n                    ) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis"],"prefix":"10.1073","volume":"107","author":[{"given":"Marie","family":"Abitbol","sequence":"first","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche 955 de G\u00e9n\u00e9tique Fonctionnelle et M\u00e9dicale, Institut National de la Recherche Agronomique, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Laurent","family":"Thibaud","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Propre de Recherche de Neurobiologie, Universit\u00e9 Paris-Est, Ecole Nationale V\u00e9t\u00e9rinaire d'Alfort, F-94700 Maisons-Alfort, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha J.","family":"Olby","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, North Carolina State University, Raleigh, NC 27606;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Hitte","sequence":"additional","affiliation":[{"name":"UMR6061 Institut de G\u00e9n\u00e9tique et D\u00e9veloppement, Centre National de la Recherche Scientifique, Universit\u00e9 de Rennes 1, F-35000 Rennes, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"Puech","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie G\u00e9n\u00e9tique, Assistance Publique\u2013H\u00f4pitaux de Paris, Universit\u00e9 Paris Descartes, F-75006 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Maurer","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche 955 de G\u00e9n\u00e9tique Fonctionnelle et M\u00e9dicale, Institut National de la Recherche Agronomique, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Pilot-Storck","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche 955 de G\u00e9n\u00e9tique Fonctionnelle et M\u00e9dicale, Institut National de la Recherche Agronomique, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"H\u00e9dan","sequence":"additional","affiliation":[{"name":"UMR6061 Institut de G\u00e9n\u00e9tique et D\u00e9veloppement, Centre National de la Recherche Scientifique, Universit\u00e9 de Rennes 1, F-35000 Rennes, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Dr\u00e9ano","sequence":"additional","affiliation":[{"name":"UMR6061 Institut de G\u00e9n\u00e9tique et D\u00e9veloppement, Centre National de la Recherche Scientifique, Universit\u00e9 de Rennes 1, F-35000 Rennes, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Brahimi","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche 955 de G\u00e9n\u00e9tique Fonctionnelle et M\u00e9dicale, Institut National de la Recherche Agronomique, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Delattre","sequence":"additional","affiliation":[{"name":"Antagene, F-69760 Limonest, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"UMR6061 Institut de G\u00e9n\u00e9tique et D\u00e9veloppement, Centre National de la Recherche Scientifique, Universit\u00e9 de Rennes 1, F-35000 Rennes, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Gray","sequence":"additional","affiliation":[{"name":"Laboratoire d'Anatomie et Cytologie Pathologique, H\u00f4pital Lariboisi\u00e8re, F-75010 Paris, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Delisle","sequence":"additional","affiliation":[{"name":"Centre de Radioth\u00e9rapie-Scanner, Ecole Nationale V\u00e9t\u00e9rinaire d'Alfort, F-94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Caillaud","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie G\u00e9n\u00e9tique, Assistance Publique\u2013H\u00f4pitaux de Paris, Universit\u00e9 Paris Descartes, F-75006 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Bernex","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche 955 de G\u00e9n\u00e9tique Fonctionnelle et M\u00e9dicale, Institut National de la Recherche Agronomique, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Jacques","family":"Panthier","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche 955 de G\u00e9n\u00e9tique Fonctionnelle et M\u00e9dicale, Institut National de la Recherche Agronomique, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Aubin-Houzelstein","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche 955 de G\u00e9n\u00e9tique Fonctionnelle et M\u00e9dicale, Institut National de la Recherche Agronomique, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Blot","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Propre de Recherche de Neurobiologie, Universit\u00e9 Paris-Est, Ecole Nationale V\u00e9t\u00e9rinaire d'Alfort, F-94700 Maisons-Alfort, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Tiret","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche 955 de G\u00e9n\u00e9tique Fonctionnelle et M\u00e9dicale, Institut National de la Recherche Agronomique, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,8,2]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.11.004"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/111.1.27"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2006.06.010"},{"key":"e_1_3_3_4_2","first-page":"259","article-title":"Kufs\u2019\u2019 disease: Diagnostic difficulties in the examination of extracerebral biopsies","volume":"47","author":"Lewandowska E","year":"2009","unstructured":"E Lewandowska, et al., Kufs\u2019\u2019 disease: Diagnostic difficulties in the examination of extracerebral biopsies. Folia Neuropathol 47, 259\u2013267 (2009).","journal-title":"Folia Neuropathol"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9075-9"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.02.099"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-9-146"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.02.010"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2006.06.005"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21015"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-10-83"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/030098588802500213"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.71.665"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1024\/0036-7281.145.8.369"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.2004.tb00161.x"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-004-0902-7"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1740-8261.2009.01655.x"},{"key":"e_1_3_3_18_2","first-page":"723","article-title":"Linkage analysis in American Staffordshire Terriers with hereditary cerebellar cortical degeneration","volume":"22","author":"Olby N","year":"2008","unstructured":"N Olby, et al., Linkage analysis in American Staffordshire Terriers with hereditary cerebellar cortical degeneration. 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