C9orf72 Hexanucleotide Repeat Analysis in Cases with Pathologically Confirmed Dementia with Lewy Bodies

Background: Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia affecting the elderly. The GGGGCC hexanucleotide expansion mutation at the C9orf72 locus has been identified as a major cause of amyotrophic lateral sclerosis and frontotemporal dementia, raising the question of whether this mutation is a factor in DLB. Furthermore, a small number of clinically diagnosed DLB patients have previously been reported to carry the pathologic C9orf72 hexanucleotide repeat expansion.

Objective: To explore whether the C9orf72 mutation is present in pathologically confirmed DLB patients.

Methods: We screened a cohort of 111 definite DLB cases with extensive Lewy body pathology for the C9orf72 hexanucleotide repeat expansion using the repeat-primed polymerase chain reaction assay.

Results: No pathogenic expansions of the C9orf72 hexanucleotide repeat were found, suggesting that there is no causal relationship between C9orf72 and DLB.

Conclusion: Our data illustrate that C9orf72 screening of clinically diagnosed DLB patients should only be considered in cases with a family history of motor neuron disease or frontotemporal dementia to distinguish between mimic diseases.