title: An inherited large-scale rearrangement in SACS associated with spastic ataxia and hearing loss.
abstract: Autosomal recessive spastic ataxia of Charlevoix-Saguenay is a neurodegenerative disorder characterized by early-onset, spastic ataxia and peripheral neuropathy, with or without mental retardation. The array of mutations in SACS has expanded worldwide after the first description in Quebec. We herein report the identification of an unconventional SACS mutation, a large-scale deletion sized approximately 1.5 Mb encompassing the whole gene, in two unrelated patients. The clinical phenotype of the patients was similar to more canonical ARSACS cases, though it is was complicated by the unusual presence of hearing loss. Our findings suggest that a "microdeletion" on chromosome 13q12 represents a novel allelic variant associated with ARSACS, stressing the need for an expanded testing in molecular diagnostic laboratories.
authors.affiliation: Molecular Medicine and Neurology, IRCCS Bambino Gesù Children's Hospital, Piazza S. Onofrio, 4 00165, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Terracciano
authors.forename: Carlo
authors.initials: C
authors.lastname: Casali
authors.forename: Gaetano S
authors.initials: GS
authors.lastname: Grieco
authors.forename: Daniela
authors.initials: D
authors.lastname: Orteschi
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Giandomenico
authors.forename: Laura
authors.initials: L
authors.lastname: Seminara
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Fabio
authors.forename: Rosalba
authors.initials: R
authors.lastname: Carrozzo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Simonati
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
authors.forename: Marcella
authors.initials: M
authors.lastname: Zollino
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000328:Adult; D001259:Ataxia / Q000235:genetics* / Q000503:physiopathology; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13; D004252:DNA Mutational Analysis; D005260:Female; D034381:Hearing Loss / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D006360:Heat-Shock Proteins; C404403:SACS protein, human