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

Abstract

Anderson–Fabry disease (FD) is an X-linked disease caused by a functional deficit of the α-galactosidase A enzyme. FD diagnosis relies on the clinical manifestations and research of GLA gene mutations. However, because of the lack of a clear genotype/phenotype correlation, FD diagnosis can be challenging. Recently, several studies have highlighted the importance of investigating DNA methylation patterns for confirming the correct diagnosis of different rare Mendelian diseases, but to date, no such studies have been reported for FD. Thus, in the present investigation, we analyzed for the first time the genome-wide methylation profile of a well-characterized cohort of patients with Fabry disease. We profiled the methylation status of about 850,000 CpG sites in 5 FD patients, all carrying the same mutation in the GLA gene (exon 6 c.901C>G) and presenting comparable low levels of α-Gal A activity. We found that, although the whole methylome profile did not discriminate the FD group from the unaffected one, several genes were significantly differentially methylated in Fabry patients. Thus, we provide here a proof of concept, to be tested in patients with different mutations and in a larger cohort, that the methylation state of specific genes can potentially identify Fabry patients and possibly predict organ involvement and disease evolution.

Host fecal DNA specific methylation signatures mark gut dysbiosis and inflammation in children affected by autism spectrum disorder

“…DNA methylation analyses were performed by using the Infinium MethylationEPIC array (Illumina, San Diego, California). As previously described 57 , 1000 ng of DNA per sample were bisulfite converted using the EZ DNA Methylation kit (Zymo Research), according to the manufacturer’s instructions. The bisulfite-treated DNA was hybridized onto the arrays and imaged with the iScan SQ instrument (Illumina).…”

A Rare Adult Primary Intracranial Sarcoma, DICER1-Mutant Identified by Epigenomic Profiling: A Case Report

“…To conduct an explorative analysis to determine the extent of the methylation differences, the methylome of the primary intracranial sarcoma, DICER1-mutant (surgically removed on December 2020), was compared with the methylome profile of a high-grade glioma. Bioinformatic analyses were performed using RnBeads scripts, as described in [15,16]. Only the CpG sites with a difference of at least 25% in DNA methylation between the primary intracranial sarcoma, DICER1-mutant, and the high-grade glioma were filtered and retained.…”