Skip to Main content Skip to Navigation
Journal articles

A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis.

Marie Abitbol 1, * Jean-Laurent Thibaud 2 Natasha Olby 3 Christophe Hitte 4 Jean-Philippe Puech 5 Marie Maurer 1 Fanny Pilot-Storck 1 Benoît Hédan 4 Stéphane Dréano 4 Sandra Brahimi 1 Delphine Delattre 6 Catherine André 4 Françoise Gray 7 Françoise Delisle 8 Catherine Caillaud 5 Florence Bernex 1 Jean-Jacques Panthier 1 Geneviève Aubin-Houzelstein 1 Stéphane Blot 2 Laurent Tiret 1, *
* Corresponding author
1 UGMC - Génétique Moléculaire et Cellulaire
2 Laboratoire de neurobiologie
3 Department of Clinical Sciences
4 IGDR - Institut de Génétique et Développement de Rennes
5 Laboratoire de biochimie et génétique moléculaire
6 Antagene
7 Service d'anatomie et cytologie pathologiques
8 Centre de radiothérapie-Scanner
Abstract : 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' 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 Arylsulfatase G (ARSG) 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.
keyword : animal model ataxia dog neurodegenerative lysosome
Document type :
Journal articles
Complete list of metadatas

Cited literature [42 references]  Display  Hide  Download
https://www.hal.inserm.fr/inserm-00511951
Contributor : Hervé de Villemeur <>
Submitted on : Thursday, August 26, 2010 - 5:15:43 PM
Last modification on : Thursday, January 14, 2021 - 11:21:39 AM
Long-term archiving on: : Thursday, December 1, 2016 - 12:56:47 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

CNRS | INRA | UNIV-PARIS5 | UNIV-PARIS7 | UNIV-RENNES1 | IGDR | BIOSIT | UR1-UFR-SVE | USPC | UNIV-RENNES | INRAE | UNIV-PARIS

Citation

Marie Abitbol, Jean-Laurent Thibaud, Natasha Olby, Christophe Hitte, Jean-Philippe Puech, et al.. A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis.. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2010, 107 (33), pp.14775-80. ⟨10.1073/pnas.0914206107⟩. ⟨inserm-00511951⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Record views

1314