title: FUS and TDP43 genetic variability in FTD and CBS.
abstract: This study aimed to evaluate genetic variability in the FUS and TDP-43 genes, known to be mainly associated with amyotrophic lateral sclerosis (ALS), in patients with the diagnoses of frontotemporal lobar degeneration (FTLD) and corticobasal syndrome (CBS). We screened the DNA of 228 patients for all the exons and flanking introns of FUS and TDP-43 genes. We identified 2 novel heterozygous missense mutations in FUS: P106L (g.22508384C>T) in a patient with behavioral variant frontotemporal dementia (bvFTD) and Q179H in several members of a family with behavioral variant FTD. We also identified the N267S mutation in TDP-43 in a CBS patient, previously only reported in 1 ALS family and 1 FTD patient. Additionally, we identified 2 previously reported heterozygous insertion and deletion mutations in Exon 5 of FUS; Gly174-Gly175 del GG (g. 4180-4185 delGAGGTG) in an FTD patient and Gly175-Gly176 ins GG (g. 4185-4186 insGAGGTG) in a patient with diagnosis of CBS. Not least, we have found a series of variants in FUS also in neurologically normal controls. In summary, we report that genetic variability in FUS and TDP-43 encompasses a wide range of phenotypes (including ALS, FTD, and CBS) and that there is substantial genetic variability in FUS gene in neurologically normal controls.
authors.affiliation: Taub Institute and Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Huey
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferrari
authors.forename: Jorge H
authors.initials: JH
authors.lastname: Moreno
authors.forename: Christopher
authors.initials: C
authors.lastname: Jensen
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Morris
authors.forename: Felix
authors.initials: F
authors.lastname: Potocnik
authors.forename: Rajesh N
authors.initials: RN
authors.lastname: Kalaria
authors.forename: Michael
authors.initials: M
authors.lastname: Tierney
authors.forename: Eric M
authors.initials: EM
authors.lastname: Wassermann
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Jordan
authors.initials: J
authors.lastname: Grafman
authors.forename: Parastoo
authors.initials: P
authors.lastname: Momeni
mesh_terms: D000368:Aged; D001480:Basal Ganglia Diseases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D057177:TDP-43 Proteinopathies / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D034702:RNA-Binding Protein FUS