title: A novel double mutation in FUS gene causing sporadic ALS.
abstract: It has been shown that mutations in the Fused in Sarcoma gene (FUS) could explain up to 5% of cases with familial amyotrophic lateral sclerosis (ALS). Our mutation analysis of FUS in a Canadian ALS patient of Chinese origin revealed an unusual novel heterozygous double point mutation (R514S/E516V) confirming that exon 15 is a mutation hot-spot. The substitutions are in cis position to each other and affect highly conserved codons in the RGG-rich region of the FUS protein. The absence of clinical signs of ALS in the relatives of the affected carrier could indicate that this mutation is incompletely penetrant or de novo. The pathologic significance of the R514S/E516V mutation was confirmed by immunohistochemistry. FUS-positive cytoplasmic inclusions were noted in a moderate number in neurons and abundantly in glial cells in the motor cortex and the brainstem. Of interest, a significant number of neuronal and glial FUS-positive inclusions were found in the tegmentum of the brainstem. Importantly, some neurons with inclusions showed retention of the normal nuclear FUS immunostaining.
authors.affiliation: University of Toronto, Department of Medicine, Centre for Research in Neurodegenerative Diseases, Toronto, ON, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Robertson
authors.forename: J
authors.initials: J
authors.lastname: Bilbao
authors.forename: L
authors.initials: L
authors.lastname: Zinman
authors.forename: L-N
authors.initials: LN
authors.lastname: Hazrati
authors.forename: S
authors.initials: S
authors.lastname: Tokuhiro
authors.forename: C
authors.initials: C
authors.lastname: Sato
authors.forename: D
authors.initials: D
authors.lastname: Moreno
authors.forename: R
authors.initials: R
authors.lastname: Strome
authors.forename: I R
authors.initials: IR
authors.lastname: Mackenzie
authors.forename: E
authors.initials: E
authors.lastname: Rogaeva
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D044466:Asian People / Q000235:genetics; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000378:metabolism / Q000473:pathology; D017354:Point Mutation / Q000235:genetics*; D034702:RNA-Binding Protein FUS / Q000235:genetics*
chemical_list: D034702:RNA-Binding Protein FUS