An inherited large-scale rearrangement in SACS associated with spastic ataxia and hearing loss.
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.
Terracciano
Alessandra
A
Molecular Medicine and Neurology, IRCCS Bambino Gesù Children's Hospital, Piazza S. Onofrio, 4 00165, Rome, Italy.
Casali
Carlo
C
Grieco
Gaetano S
GS
Orteschi
Daniela
D
Di Giandomenico
Silvia
S
Seminara
Laura
L
Di Fabio
Roberto
R
Carrozzo
Rosalba
R
Simonati
Alessandro
A
Stevanin
Giovanni
G
Zollino
Marcella
M
Santorelli
Filippo M
FM
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
D006360:Heat-Shock Proteins; C404403:SACS protein, human