Co-occurrence of the C9ORF72 expansion and a novel GRN mutation in a family with alternative expression of frontotemporal dementia and amyotrophic lateral sclerosis

Abstract

The C9ORF72 repeat expansion is the major cause of frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and FTLD-ALS. In the reported pedigree, the 47-year old proband, presenting a four-year history of frontotemporal dementia, carried the C9ORF72 expansion plus a novel GRN p.Cys246X mutation. The father and a paternal uncle, harboring the C9ORF72 expansion only, had died by pure ALS with onset at 63 and 76 years, respectively. The case report and a review of the literature emphasize that phenotypical variations of the FTLD-ALS spectrum could be due to digenic inheritance.

Keywords: Amyotrophic lateral sclerosis (ALS); C9ORF72; FTLD-ALS; GRN; frontotemporal lobar degeneration (FTLD).