The secondary epimutation of our epi-cblC cases is located in a trio of genes (reverse CCDC163P–forward MMACHC–reverse PRDX1) (Fig. 6d, e), in a bidirectional promoter in the head-to-head sense–antisense gene pair (SAGP) constituted by CCDC163P and MMACHC. The forced antisense transcription of MMACHC resulted from the skipping of the last exon of PRDX1. This skipping was the causative defect that produced the epimutation since the silencing of PRDX1 decreased the methylation of exon 1 of MMACHC and the promoter, and restored the transcription of MMACHC, in WG-3838 and MeWo-LC1 cells. The gene discussed is MMACHC; the disease is methylmalonic aciduria and homocystinuria type cblC.