Short communicationA PCR-based protocol to accurately size C9orf72 intermediate-length alleles

- Large GGGGCC expansions in C9orf72 gene are frequent genetic cause of ALS and FTLD.
- Intermediate GGGGCC expansions in C9orf72 gene are also associated with ALS and FTLD.
- Intermediate-length alleles are also associated with other neurodegenerative diseases.
- Current PCR-based methods may lead to incorrect sizing of intermediate-length alleles.
- Our PCR-based protocol exactly sizes C9orf72 intermediate-length alleles.

Although large expansions of the non-coding GGGGCC repeat in C9orf72 gene are clearly defined as pathogenic for Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD), intermediate-length expansions have also been associated with those and other neurodegenerative diseases. Intermediate-length allele sizing is complicated by intrinsic properties of current PCR-based methodologies, in that somatic mosaicism could be suspected. We designed a protocol that allows the exact sizing of intermediate-length alleles, as well as the identification of large expansions.