C9orf72 Hexanucleotide Repeat Expansions as the Causative Mutation for Chromosome 9p21–Linked Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Objective

To further assess the presence of a large hexanucleotide repeat expansion in the first intron of the C9orf72 gene identified as the genetic cause of chromosome 9p21–linked amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD) in 4 unrelated families with a conclusive linkage to c9ALS/FTD.

Design

A repeat-primed polymerase chain reaction assay.

Setting

Academic research.

Participants

Affected and unaffected individuals from 4 ALS/FTD families.

Main Outcome Measure

The amplified C9orf72 repeat expansion.

Results

We show that the repeat is expanded in and segregated perfectly with the disease in these 4 pedigrees.

Conclusion

Our findings further confirm the C9orf72 hexanucleotide repeat expansion as the causative mutation for c9ALS/FTD and strengthen the hypothesis that ALS and FTD belong to the same disease spectrum.