Psychosis associated with expansions in the C9orf72 gene: the influence of a 10 base pair gene deletion

We previously reported1 that expansionsin the C9orf7 2 gene, identified by Southern blotting or using a repeat primed PCR assay,2 may go undetected using an alternative, standard PCR assay.3 We attributed this discrepancy to a 10 base pair deletion adjacent to the expansionwhich was presumed to interfere with genotyping.1 To determine the possible clinical and pathological relevance of the deletion, we compared patients in whom the C9orf72 expansionwas detected using the Renton3 assay (C9 reference group) with those carrying an expansionnot detected by this method (deletion group). The criteria for inclusion in the study were: (A) patients had been investigated and diagnosed with dementia within a single, specialist dementia clinic, (B) they had donated DNA as part of an ethically approved study into the molecular genetics of dementia and (C) expansionsin the C9orf72gene were identified using one or more standard procedures.1–3 An additional patient, in whom pathological examination showed p62 positive neuronal inclusions immunoreactive for the dipeptide repeat proteins, poly-GA, poly-GP and poly-GR, was also included since such histological findings are considered pathognomonicof the presence of an expansionin C9orf72.4 …