Screening a UK amyotrophic lateral sclerosis cohort provides evidence of multiple origins of the C9orf72 expansion

• DOI: 10.1016/j.neurobiolaging.2014.07.037
• Publication Date: 2014-08-01T16:23:29Z
• Authors: Pietro Fratta; James M. Polke; Jia Newcombe; Sarah Mizielinska; Tammaryn Lashley; Mark Poulter; Jon Beck; Elisavet Preza; Anny Devoy; Katie Sidle; Robin Howard; Andrea Malaspina; Richard W. Orrell; Jan Clarke; Ching-Hua Lu; Kin Mok; Toby Collins; Maryam Shoaii; Tina Nanji; Selina Wray; Gary Adamson; Alan Pittman; Alan E. Renton; Bryan J. Traynor; Mary G. Sweeney; Tamas Revesz; Henry Houlden; Simon Mead; Adrian M. Isaacs; Elizabeth M.C. Fi...
• Keywords: C9ORF72

An expanded hexanucleotide repeat in the C9orf72 gene is most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). Although 0–30 repeats are present general population, expansions >500 associated with C9ALS/FTD. Large C9ALS/FTD share a haplotype whether these derive from single founder or occur more frequently on predisposing yet to be determined relevant disease pathomechanisms. Furthermore, although cases carrying 50–200 have been described, their role pathogenic threshold remain identified carry importance for diagnostics counseling. We clinical data UK ALS cohort report detailed molecular study an atypical somatically unstable expansion 90 repeats. Our results across different tissues provide evidence pathogenicity this number by showing they can expand central nervous system well characterized range. support occurrence multiple events