C9orf72 Gene Expression in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

We studied the expression of C9orf72 gene in pathologies associated with hexanucleotide repeats expansion in this gene: frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The study included 7 patients with hexanucleotide repeats expansion in the C9orf72 gene and 9 patients of the control group. The expression of C9orf72 mRNA was evaluated in blood leukocytes by real-time PCR. Methylation of CpG-sites in C9orf72 promotor region was evaluated by DNA sequencing after bisulfite conversion. A 2-fold decrease in the C9orf72 gene expression was found in patients with hexanucleotide repeats expansion in comparison with controls, though the difference did not reach statistical significance due to small sample size. The highest expression was shown for ALS in comparison with FTD and FTD-ALS phenotype. A trend to inverse correlation between C9orf72 mRNA level and promoter methylation of this gene as well as between mRNA level and age of disease onset was demonstrated.