title: A novel SACS gene mutation in a Tunisian family.
abstract: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a distinct form of hereditary early-onset spastic ataxia. In 2000, the causative gene, SACS, encoding the protein sacsin, was identified in Quebec patients. The open reading frame (ORF) of SACS was initially reported to contain 11,487 bp and to be encoded by a single gigantic exon. Recently, eight additional exons upstream of the original ORF were found (ENST00000382298). We report four Tunisian ARSACS patients homozygous for a novel mutation in SACS exon 9 gene, c.12846_12850delAGAG. This mutation is localized upstream from the DnaJ domain leading to the loss of this domain, suggesting that the disease is associated with loss of critical chaperone function of sacsin.
authors.affiliation: Laboratoire de Neurobiologie Moléculaire et de Neuropathologie, Institut National de Neurologie, 1007 la Rabta, Tunis, Tunisia. yosr23@hotmail.com
authors.forename: Yosr
authors.initials: Y
authors.lastname: Bouhlal
authors.forename: Ghada
authors.initials: G
authors.lastname: El Euch-Fayeche
authors.forename: Fayçal
authors.initials: F
authors.lastname: Hentati
authors.forename: Rim
authors.initials: R
authors.lastname: Amouri
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics; D009128:Muscle Spasticity / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D013132:Spinocerebellar Degenerations / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D014416:Tunisia / Q000208:ethnology
chemical_list: D005819:Genetic Markers; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; C404403:SACS protein, human