Table 1 Summary of the main characteristics of the evaluated studies

From: DNA methylation impact on Fabry disease

References Samples Type of sample Method Main findings
Redonnet-Vernhet et al. [15] 2 FD women Peripheral blood leukocytes; Fibroblasts HUMARA assay Unbalanced XCI in monozygotic twins’ fibroblasts in opposite direction. This is the first documented case of female twins discordant for FD
Maier et al. [19] 28 FD women Blood HUMARA assay Fabry heterozygous females showed a random X inactivation and no significant correlation was found between X inactivation patterns and clinical phenotype
Elstein et al. [20] 77 FD women Peripheral blood leukocytes HUMARA assay XCI did not correlate with signs and symptoms of classic Fabry disease
Hübner et al. [51] 9 FD patients Peripheral blood leukocytes CALCR Methylation-specific PCR- High-resolution melting
CALCR sequencing
A specific CpG of autosomal CALCR gene is differentially methylated in ERT treated and non-ERT-treated FD patients indicating that this CpG could be an epigenetic biomarker of FD
Echevarria et al. [18] 56 FD women Peripheral blood; Mouth epithelial cells; skin biopsy; Urine HUMARA assay XCI significantly impacted the phenotype and natural history of FD in females, supporting the correlation between XCI and clinical phenotype
Hossain et al. [44] 4 FD women Peripheral blood; spinal fluid GLA Methylation-sensitive restriction enzymes analyses
GLA Bisulfite Sanger sequencing
Allele-specific GLA methylation correlated with the severity of FD phenotype
Juchniewicz et al. [21] 12 FD women Saliva HUMARA assay XCI pattern did not correlate with Fabry disease severity scores
Hossain et al. [46] 36 FD women Peripheral blood; skin fibroblasts GLA Methylation-sensitive restriction enzymes analyses
GLA Bisulfite Sanger sequencing
Methylation of the GLA non-mutated allele was proportionally correlated with the clinical severity score (FASTEX score)
Yanagisawa et al. [45] 4 FD women Fibroblast from Skin tissue Allele-specific GLA expression (RT-PCR) mRNA expression level of the GLA mutant allele correlated with disease severity
De Riso et al. [55] 3 FD women Peripheral blood High coverage-amplicon bisulfite sequencing (HC-ABS) versus HUMARA Substantial concordance in direction and entity of the methylation imbalance between AR and GLA genes. Clearly distinct allele-specific epiallele profiles were obtained by epiallele distribution analysis
Rossanti et al. [56] 9 FD women Blood leukocytes; Urine sediments HUMARA assay
GLA Ultra-deep targeted RNA Sequencing
Skewed XCI explained the severity of FD in only limited number of female cases