Characterization of the repeat expansion size in C9orf72 in amyotrophic lateral sclerosis and frontotemporal dementia

HexanucleotiderepeatexpansionswithintheC9orf72genearethemostimportantgeneticcauseofamyotrophiclateralsclerosis(ALS)andfrontotemporaldementia(FTD).Thedifficultyofdevelopingaprecisemethodtode-terminetheexpansionsizehashamperedthestudyofpossiblecorrelationsbetweenthehexanucleotiderepeatnumberandclinicalphenotype.Herewecharacterize,throughanewnon-radioactiveSouthernblotprotocol,theexpansion size range in a series of 38 ALS and 22 FTD heterozygous carriers of>30 copies of the repeat.Maximum, median and modal hexanucleotide repeat number were higher in ALS patients than in FTD patients(P < 0.05 in all comparisons). A higher median number of repeats correlated with a bigger range of repeatsizes(Spearman’sr5 0.743,P 5 1.05 3 10