Table 1 Summary of the main characteristics of the evaluated studies
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 |