Fig. 2

Analyses of DNA methylation in the 11 epi-cblC patients. a Epi-Manhattan plot reporting the epigenome-wide association study comparing the 11 epi-cblC subjects with controls. The −log10 P-value reports on the t-test comparing the β values of epi-cblC subjects and controls. The horizontal line indicates a P-value threshold of 1 × 10^–90. The top significant locus corresponds to the CpG island (CpG:33) on the CCDC163/MMACHC bidirectional promoter in chromosome 1. b Methylation levels of the CCDC163/MMACHC bidirectional promoter in the epi-cblC patients carrying the heterozygous PRDX1:c.515-1G > T variant and controls. The horizontal lines correspond to β value thresholds of 0.2, below which the CpG probe is considered to be fully unmethylated. Above 0.6 the CpG probe is considered as fully methylated. A β value between 0.2 and 0.6 indicates a hemimethylated CpG probe. c Methylation levels of the CCDC163/MMACHC bidirectional promoter in the homozygous epi-cblC patient (Pt 11) and his parents. All the reported CpG probes exhibit a hemimethylated profile in the parents and a full-methylated profile in the index case harbouring the PRDX1 splice variant (c.515-1G > T) at the homozygous state