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

Jay P Ross; Claire S Leblond; Hélène Catoire; Kathryn Volkening; Michael Strong; Lorne Zinman; Janice Robertson; Patrick A Dion; Guy A Rouleau

doi:10.1212/NXG.0000000000000317

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

Neurol Genet. 2019 Mar 19;5(2):e317. doi: 10.1212/NXG.0000000000000317. eCollection 2019 Apr.

Authors

Jay P Ross¹, Claire S Leblond¹, Hélène Catoire¹, Kathryn Volkening¹, Michael Strong¹, Lorne Zinman¹, Janice Robertson¹, Patrick A Dion¹, Guy A Rouleau¹

Affiliation

¹ Department of Human Genetics (J.P.R., G.A.R.), McGill University, Montréal, Quebec, Canada; Montreal Neurological Institute and Hospital (J.P.R., H.C., P.A.D., G.A.R.), McGill University, Montréal, Quebec, Canada; Pasteur Institute (C.S.L.), University Paris Diderot, Sorbonne Paris Cité, Paris, France; Department of Neurology and Neurosurgery (H.C., P.A.D., G.A.R.), McGill University, Montréal, Quebec, Canada; Department of Clinical Neurological Sciences and Robarts Research Institute (K.V., M.S.A.N.N.), Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Sunnybrook Health Sciences Centre (L.Z.); and Tanz Centre for Research in Neurodegenerative Diseases (J.R.), University of Toronto, Toronto, Ontario, Canada.

Abstract

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.