Somatic expansion of the C9orf72 hexanucleotide repeat does not occur in ALS spinal cord tissues

Objective To test for somatic C9orf72 hexanucleotide repeat expansion (HRE) and hexanucleotide repeat length instability in the spinal cord of amyotrophic lateral sclerosis (ALS) cases. Methods Whole and partial spinal cords of 19 ALS cases were dissected into transversal sections (5 mm thick). The presence of C9orf72 HRE was tested in each independent section using RepeatPrimed PCR and amplicon-size genotyping. Index measures for the testing of mosaicism were obtained through serial dilutions of genomic DNA from an individual carrying a germline C9orf72 HRE in the genomic DNA of an individual without a C9orf72 HRE. Results None of the sections examined supported the presence of a subpopulation of cells with a C9orf72 HRE. Moreover, the C9orf72 hexanucleotide repeat lengths measured were identical across all the spinal cord sections of each individual patient. Conclusions We did not observe somatic instability of the C9orf72 HRE in disease relevant tissues of ALS cases.