Table 1.
DNAme studies in DM1, DM2 and control (CTR) individuals.
| Disease Form | Tissue | Sample Size | Genomic Context (DMPK Gene) |
Method of Analysis | Analysis Outcome | Reference |
|---|---|---|---|---|---|---|
| CDM1; Adult |
Dura mater, skeletal muscle, skin biopsies and white blood cells | 30 DM1 | Upstream region of (CTG)n repeats, corresponding to the genomic SacI-HindIII fragment carrying exons 11–15 |
Methylation-sensitive restriction enzymes digestion | Hypermethylation in intron 12 at restriction sites of SacII and HhaI in CDM1 patients |
[35] |
| DM1 foetuses; DM1 adults; Transgenic DM1 mice |
Different source | 13 DM1 vs. 3 CTRs |
CTCF binding sites upstream and downstream of the CTG repeats | Bisulphite-sequencing PCR and methylation-sensitive restriction enzymesdigestion | Hypermethylation of upstream sequences in DM1 individuals. In DM1, mice methylation pattern was present up- and down-stream of the CTG array | [40] |
| Childhood-onset; Juvenile/adult-onset; CDM1 with uninterrupted CTG expansions; DM1 “atypical” |
Whole blood |
66 DM1 including 9 patients with VRs vs. 30 CTRs |
DNA sequences (including CTCF-1 and CTCF-2) in 5′ and in 3′ end regions of the CTG array | MS-HRM | Hypermethylation of upstream sequences in CDM1 and childhood-onset patients with large uninterrupted (CTG)n expansions, significantly associated with maternal transmission. First evidence that DM1 patients with VRs show a distinctive hypermethylation pattern at 3′ end of the CTG array | [27] |
| Premutated DMPK alleles containing VRs |
Whole blood |
Three-generation Italian family | DNA sequences (including CTCF-1 and CTCF-2) in 5′ and in 3′ end regions of CTG array | Pyrosequencing | Absence of an in cis effect of the (CCG)n interruptions on the methylation of the DM1 locus | [43] |
| DM1-Affected hESC Line Collection | hESCs | 14 DM1 | DNA sequence spanning from exon 11 to the CTG repeats | Pyrosequencing | Marked increase in methylation levels of the expanded allele | [39] |
| Late-onset; Adult; Juvenile; Childhood |
Whole blood |
92 DM1 vs. 10 CTRs |
Upstream (CTCF1) and downstream (CTCF2) regions | Sanger Sequencing and Massive Parallel Sequencing | DNAme levels of both CTCF sites higher in CDM1 than in non-CDM1 patients | [34] |
| Adult-onset; DM1 “atypical” |
Whole blood |
90 DM1 including 8 patients with VRs | CpG sites upstream and downstream of the (CTG)n expansion | Pyrosequencing | DNAme levels upstream of the (CTG)n expansion were correlated with CTG repeat length, and the presence of a VRs was associated with higher DNAme levels compared to pure CTG array | [42] |
| Adult-onset; DM1 “atypical” |
Whole blood |
115 DM1 including 12 patients with VRs |
Downstream region (no CTCF binding sites) of the (CTG)n repeats | Pyrosequencing | Patients with VRs alleles had distinctive DNAme and cognitive profiles | [28] |
| Noncongenital DM1 |
Whole blood |
68 DM1 vs. 73 CTRs |
Upstream and downstream regions (no CTCF binding sites) of the (CTG)n repeats | Pyrosequencing | Hypermethylation of both upstream and downstream regions | [44] |
| DM2 | Whole blood |
72 DM2 vs. 50 CTRs |
CpG islands in the 5′ promoter region and in the region 3′ of the [CCTG]n repetitions | Pyrosequencing | No significant differences in the methylation profile between DM2 patients and CTRs | [45] |
| Skeletal muscle | 7 DM2 vs. 7 CTRs |
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| Skeletal muscle | 7 DM2 vs. 7 CTRs |