Epigenomic signature of adrenoleukodystrophy predicts compromised oligodendrocyte differentiation

Brain Pathology
Agatha SchlüterAurora Pujol

Abstract

Epigenomic changes may either cause disease or modulate its expressivity, adding a layer of complexity to mendelian diseases. X-linked adrenoleukodystrophy (X-ALD) is a rare neurometabolic condition exhibiting discordant phenotypes, ranging from a childhood cerebral inflammatory demyelination (cALD) to an adult-onset mild axonopathy in spinal cords (AMN). The AMN form may occur with superimposed inflammatory brain demyelination (cAMN). All patients harbor loss of function mutations in the ABCD1 peroxisomal transporter of very-long chain fatty acids. The factors that account for the lack of genotype-phenotype correlation, even within the same family, remain largely unknown. To gain insight into this matter, here we compared the genome-wide DNA methylation profiles of morphologically intact frontal white matter areas of children affected by cALD with adult cAMN patients, including male controls in the same age group. We identified a common methylomic signature between the two phenotypes, comprising (i) hypermethylation of genes harboring the H3K27me3 mark at promoter regions, (ii) hypermethylation of genes with major roles in oligodendrocyte differentiation such as MBP, CNP, MOG and PLP1 and (iii) hypomethylation of immune-associ...Continue Reading

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Citations

Oct 1, 2020·Annals of Clinical and Translational Neurology·Bettina ZierfussJohannes Berger
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Aug 13, 2021·Journal of Proteome Research·Amelie S Lotz-HavlaSøren W Gersting

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Datasets Mentioned

BETA
GSE78218
E-MEXP-3288

Methods Mentioned

BETA
histone acetylation
Assay
PCR
protein assay
MDS
Chip-seq
GTPase

Software Mentioned

PyroMark assay design
Limma
pROC
Genome Studio
R
XALD
Bioconductor
glmnet

Related Concepts

Related Feeds

Adrenoleukodystrophy

Adrenoleukodystrophy (ALD), the most frequent peroxisomal disorder, is an X-linked disorder caused by a defect in the metabolism of long chain fatty acids leading to demyelination, neurodegeneration, and death. Here is the latest research.