Fig. 2
A Epi-Manhattan plot reporting the results of the epigenome-wide association study that compared 17 patients with MMACHC epimutation (epi-cblC disease, isolated MMACHC epimutation, biallelic MMACHC epimutation) with controls. The − log10 P-value reports the t-test that compared the mean β values between the two groups. The horizontal line indicates a P-value threshold of 1 × 10−100. The top significant hit in chromosome 1 corresponds to the CpG island (CpG:33) on the bidirectional promoter of CCDC163–MMACHC and the CpG island (CpG:51) on the promoter region of the TESK2 gene. B Epigrams reporting the methylation levels of the top CpG probes from the epigenome-wide association study results that compared 17 patients with MMACHC epimutation (epi-cblC disease, isolated MMACHC epimutation, biallelic MMACHC epimutation) (black bars) with controls (gray bars). 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 fully methylated. A β value between 0.2 and 0.6 indicates a hemimethylated CpG probe. All the CpG probes located in CpG islands CpG:33 (CCDC163P–MMACHC bidirectional promoter), upstream the 5’ end of the TESK2 promoter, and the CpG:51 (TESK2 promoter) were fully unmethylated among controls and exhibited a hemimethylated profile among cases