Fig. 1

Identification and characterization of constitutional MLH1 epigenetic mosaicism in case 29. a Methylation analysis by MS-MCA of the MLH1 promoter C-region in blood DNA from case 29. The patient shows levels of methylation around 1%. b Family pedigree from case 29. The epimutation carrier is indicated by an arrow. Circles, females; squares, males; filled, cancer affected; vertical line at center, not otherwise specified. Cancer location and age at diagnosis are indicated. Generations are indicated on the left margin in Roman numerals. c Methylation analysis by pyosequencing of the MLH1 promoter C-region in blood DNA from case 29 and one healthy control. Each CpG is numbered according its position relative to the translation initiation codon. d Clonal bisulfite sequencing of the MLH1 promoter in PBL DNA from case 29. Each horizontal line represents a specific allele. CpG dinucleotides are depicted by circles. Black and white circles indicate methylated and unmethylated CpG sites, respectively. The allele at rs1800734 (c.-93G>A) is indicated as A or G. Methylation in case 29 is confined to the G allele. Each CpG analyzed is numbered according to its position relative to the translation initiation codon