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

Objective To test for somatic C9orf72hexanucleotide repeat expansion (HRE) and hexanucleotide repeat length instability in the spinal cord of amyotrophic lateral sclerosis(ALS) cases. MethodsWhole and partial spinal cords of 19 ALS cases were dissected into transversal sections (5 mm thick). The presence of C9orf72HRE was tested in each independent section using RepeatPrimed PCR and amplicon-size genotyping. Index measures for the testing of mosaicism were obtained through serial dilutionsof genomic DNAfrom an individual carrying a germline C9orf72HRE in the genomic DNAof an individual without a C9orf72HRE. Results None of the sections examined supported the presence of a subpopulation of cells with a C9orf72HRE. Moreover, the C9orf72hexanucleotide repeat lengths measuredwere identical across all the spinal cord sections of each individual patient. Conclusions We did not observe somatic instability of the C9orf72HRE in disease relevant tissues of ALS cases.