title: Two novel homozygous SACS mutations in unrelated patients including the first reported case of paternal UPD as an etiologic cause of ARSACS.
abstract: Autosomal recessive spastic ataxia of Charlevoix-Saguenay, more commonly known as ARSACS, is an early-onset cerebellar ataxia with spasticity, amyotrophy, nystagmus, dysarthria, and peripheral neuropathy. SACS is the only gene known to be associated with the ARSACS phenotype. To date, 55 mutations have been reported; of these, only five in Italian patients. We found two novel homozygous nonsense mutations in the giant exon of SACS gene in two unrelated patients with classical ARSACS phenotype. Characterization of the homozygous nature of the mutations through genotyping of the parents, quantitative DNA analysis and indirect STS studies permitted us to confirm in one of the cases that uniparental isodisomy of the paternal chromosome 13 carrying the mutated SACS gene played an etiologic role in the disease.
authors.affiliation: Genetics Unit, Mauro Baschirotto Institute for Rare Diseases-B.I.R.D. Foundation, Costozza di Longare, Vicenza, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Anesi
authors.forename: Paola
authors.initials: P
authors.lastname: de Gemmis
authors.forename: Massimo
authors.initials: M
authors.lastname: Pandolfo
authors.forename: Uros
authors.initials: U
authors.lastname: Hladnik
mesh_terms: D000328:Adult; D002882:Chromosomes, Human, Pair 13; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006360:Heat-Shock Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D009128:Muscle Spasticity / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020754:Spinocerebellar Ataxias / Q000151:congenital / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D024182:Uniparental Disomy / Q000235:genetics*
chemical_list: D006360:Heat-Shock Proteins; C404403:SACS protein, human