Genome-wide DNA methylation analysis of a cohort of 41 patients affected by Oculo-auriculo-vertebral spectrum (OAVS).

ABSTRACT: Oculo-auriculo-vertebral spectrum (OAVS; OMIM 164210) is a rare developmental disorder originating from abnormal development of the first and second branchial arch. The clinical phenotype is extremely heterogeneous with ear anomalies, hemifacial microsomia, ocular defects, and vertebral malformations being the main features. MYT1, AMIGO2 and ZYG11B gene variants having been reported in a few OAVS patients, but the etiology of the disease remains largely unknown. A multifactorial origin of the OAVS has been proposed, including the involvement of environmental or epigenetic mechanisms. To identify the epigenetic mechanisms contributing to OAVS, we evaluated the DNA-methylation profile of 41 affected patients by using a BeadChip 450K genome-wide approach. The analysis was first carried out at a group level by comparing the OAVS group methylation profile to the control group (n=48) revealing a slight epigenetic variation in a number of genes implicated in biological processes involving basic chromatin dynamics such as DNA packaging, chromatin assembly, protein-DNA organization, and gene silencing in patients compared to controls . A subsequent analysis focused on searching for Stochastic Epigenetic Variations (SEV) in individual profiles identified an increased number of SEV in OAVS patients compared to controls. Although no recurrent deregulated enriched region was evidenced, isolated patients harboring suggestive epigenetic variations, including changes in imprinted domains, were identified. The recognition of a different DNA methylation pattern in OAVS patients and the identification of isolated patients with suggestive epigenetic variations provide consistent evidences for the contribution of epigenetic mechanisms to the etiology of this complex and heterogeneous disorder.

ORGANISM(S): Homo sapiens

PROVIDER: GSE152204 | GEO | 2021/02/04

REPOSITORIES: GEO