|Number of repeats||Counts (alleles)||Percentage|
Overview of repeats
Expansions in C9orf72 gene are linked to the amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and is a common cause for ALS, FTD and FTD-ALS diseases, accounting for 11%, 4-29% and 17-28% of cases, respectively (Van Mossevelde et al., 2018). In addition, the frequency is higher for familial cases of the diseases (38% in ALS, 29% in FTD and up to 88% in FTD-ALS) (Van Mossevelde et al., 2018). Repeat expansions have been also detected in patients diagnosed with other neurodegenerative diseases, such as Alzheimer's, Parkinson, and Huntington disease-like disease (Beck et al., 2013; Cacace et al., 2013; Lesage et al., 2013; Woollacott & Mead, 2014).
Normal and pathogenic ranges are not very well defined and varies. In a healthy population, repeats usually range from 1 to 23, whereas 2 repeats is the most common allele (Rutherford et al., 2012). However, larger alleles, such as ones with 35 (Simón-Sánchez et al., 2012) repeats or ever over 400 (Beck et al., 2013) have been also observed in healthy individuals. Despite that, the pathogenic range is generally considered above 30 repeats and likely reaching up to thousands of repeats, but the minimum length is not well defined (Woollacott & Mead, 2014). It is also suggested that alleles between 30-45 should not be considered as pathogenic (Kaivola et al., 2019), but this could be population dependant. Most expansions in patients are at least several hundred repeats long (Van Mossevelde et al., 2017). The intermediate range is often is defined as either 7-30 or 20-30 repeats and thought to contribute to neurodegenerative diseases (Kaivola et al., 2019), but not so well defined either.