title: Screening for C9ORF72 repeat expansion in FTLD.
abstract: In the present study we aimed to determine the prevalence of C9ORF72 GGGGCC hexanucleotide expansion in our cohort of 53 frontotemporal lobar degeneration (FTLD) patients and 174 neurologically normal controls. We identified the hexanucleotide repeat, in the pathogenic range, in 4 (2 bv-frontotemporal dementia (FTD) and 2 FTD-amyotrophic lateral sclerosis [ALS]) out of 53 patients and 1 neurologically normal control. Interestingly, 2 of the C9ORF72 expansion carriers also carried 2 novel missense mutations in GRN (Y294C) and in PSEN-2(I146V). Further, 1 of the C9ORF72 expansion carriers, for whom pathology was available, showed amyloid plaques and tangles in addition to TAR (trans-activation response) DNA-binding protein (TDP)-43 pathology. In summary, our findings suggest that the hexanucleotide expansion is probably associated with ALS, FTD, or FTD-ALS and occasional comorbid conditions such as Alzheimer's disease. These findings are novel and need to be cautiously interpreted and most importantly replicated in larger numbers of samples.
authors.affiliation: Laboratory of Neurogenetics, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferrari
authors.forename: Kin
authors.initials: K
authors.lastname: Mok
authors.forename: Jorge H
authors.initials: JH
authors.lastname: Moreno
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cosentino
authors.forename: Jill
authors.initials: J
authors.lastname: Goldman
authors.forename: Pietro
authors.initials: P
authors.lastname: Pietrini
authors.forename: Richard
authors.initials: R
authors.lastname: Mayeux
authors.forename: Michael C
authors.initials: MC
authors.lastname: Tierney
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kapogiannis
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Jicha
authors.forename: Jill R
authors.initials: JR
authors.lastname: Murrell
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.forename: Eric M
authors.initials: EM
authors.lastname: Wassermann
authors.forename: Jordan
authors.initials: J
authors.lastname: Grafman
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Edward D
authors.initials: ED
authors.lastname: Huey
authors.forename: Parastoo
authors.initials: P
authors.lastname: Momeni
mesh_terms: D000368:Aged; D000073885:C9orf72 Protein; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000453:epidemiology* / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D011506:Proteins / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D005819:Genetic Markers; D011506:Proteins