title: p62/SQSTM1 analysis in frontotemporal lobar degeneration.
abstract: Mutations in the gene p62/SQSTM1 have been reported as a relatively rare cause of frontotemporal lobar degeneration (FTLD). To establish whether this was the case for cases of FTLD from the United Kingdom, we sequenced the sequenced the entire open reading frame of this gene in a large cohort of patients. We identified 3 novel mutations in p62/SQSTM1 in 4 patients. One of these was a premature stop codon that removed the last 101 amino acids of the protein that presumably has a negative effect on protein function. Another mutation was also found in a case with a repeat expansion mutation in C9orf72 confirmed by Southern blot. These findings confirm a role of p62/SQSTM1 as a cause of FTLD.
authors.affiliation: Faculty of Medical and Human Sciences, Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Miller
authors.affiliation: Faculty of Medical and Human Sciences, Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Rollinson
authors.affiliation: Faculty of Medical and Human Sciences, Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.
authors.forename: Janis Bennion
authors.initials: JB
authors.lastname: Callister
authors.affiliation: Faculty of Medical and Human Sciences, Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Young
authors.affiliation: Institute of Brain, Behaviour and Mental Health, Salford Royal Hospital NHS Foundation Trust, Salford, UK.
authors.forename: Jenny
authors.initials: J
authors.lastname: Harris
authors.affiliation: Institute of Brain, Behaviour and Mental Health, Salford Royal Hospital NHS Foundation Trust, Salford, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Gerhard
authors.affiliation: Institute of Brain, Behaviour and Mental Health, Salford Royal Hospital NHS Foundation Trust, Salford, UK.
authors.forename: David
authors.initials: D
authors.lastname: Neary
authors.affiliation: Institute of Brain, Behaviour and Mental Health, Salford Royal Hospital NHS Foundation Trust, Salford, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Richardson
authors.affiliation: Institute of Brain, Behaviour and Mental Health, Salford Royal Hospital NHS Foundation Trust, Salford, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Snowden
authors.affiliation: Institute of Brain, Behaviour and Mental Health, Salford Royal Hospital NHS Foundation Trust, Salford, UK.
authors.forename: David M A
authors.initials: DM
authors.lastname: Mann
authors.affiliation: Faculty of Medical and Human Sciences, Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK. Electronic address: SPB@Manchester.ac.uk.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Pickering-Brown
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000235:genetics; D000073885:C9orf72 Protein; D018389:Codon, Nonsense / Q000235:genetics; D015331:Cohort Studies; D042622:DNA Repeat Expansion / Q000235:genetics; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D011506:Proteins / Q000235:genetics; D000071456:Sequestosome-1 Protein; D006113:United Kingdom
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000596:Amino Acids; D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D018389:Codon, Nonsense; D011506:Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein
keywords: C9orf72; FTLD; Frontotemporal lobar degeneration; SQSTM1; p62