The top up-DPpGCs were shed by the following gene loci: Large1 (-log10p-value = 5.7, FC = 5.2), Csmd1 (-log10p-value = 5.4, FC = 5.9), Sox5 (− log10p-value = 5.2, FC = 6.3), Cdh4 (− log10p-value = 5.2, FC = 5.7), Ntm (− log10p-value = 4.8, FC = 4.9), and Galnt2l (− log10p-value = 4.3, FC = 5.3), as indicated in Fig. 3C. EccDNA release from each of these 6 hotspot loci was consistently detected in at least 8 out of the 9 ALS samples investigated (Fig. 3C). This evidence concerns the gene CDH4 and amyotrophic lateral sclerosis.