Methylome Profiling in Fabry Disease in Clinical Practice: A Proof of Concept

Int J Mol Sci. 2022 Oct 11;23(20):12110. doi: 10.3390/ijms232012110.

PMID: 36292965

Teodolinda Di Risi, Mariella Cuomo, Roberta Vinciguerra

Highlights: The methylation state of specific genes can potentially identify Fabry patients and possibly predict organ involvement and disease evolution.

Abstract

Background: The X-linked disease Anderson-Fabry disease (FD) is brought on by a deficiency in the enzyme α-galactosidase A. The clinical signs and studies of GLA gene mutations are used to diagnose FD. However, FD diagnosis can be difficult because there isn't a clear correlation between genotype and phenotype. Recently, several studies have highlighted the significance of examining DNA methylation patterns for confirming the correct diagnosis of various rare Mendelian diseases, however, to date, no such studies have been reported for FD.

Objective: As a result, in the current study, we examined for the first time the genome-wide methylation profile of a cohort of patients with Fabry disease who were well-characterized. In 5 FD patients with the identical GLA gene mutation (exon 6 c.901C>G) and comparable low levels of α-Gal A activity, we assessed the methylation status of about 850,000 CpG sites.

Conclusion: Even though the entire methylome profile was unable to distinguish between the FD group and the unaffected group, we discovered that several genes in Fabry patients had significantly different levels of methylation. The methylation status of particular genes may therefore be used to identify Fabry patients and maybe predict organ involvement and disease progression. This proof of concept will be investigated in individuals with other mutations and in a larger cohort.

Keywords: Fabry disease, Mendelian disease, methylome