p62/SQSTM1 analysis in frontotemporal lobar degeneration

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.