Genet Med. 2023 Apr 27:100871. doi: 10.1016/j.gim.2023.100871. Online ahead of print.
ABSTRACT
PURPOSE: HNRNPU haploinsufficiency is associated with Developmental and Epileptic Encephalopathy 54. This neurodevelopmental disorder is characterized by developmental delay, intellectual disability, speech impairment, and early onset epilepsy. We performed genome-wide DNA methylation (DNAm) analysis in a cohort of individuals to develop a diagnostic biomarker and gain functional insights into the molecular pathophysiology of HNRNPU-related disorder.
METHODS: DNAm profiles of individuals carrying pathogenic HNRNPU variants, identified through an international multi-center collaboration, were assessed using Infinium Methylation EPIC arrays. Statistical and functional correlation analyses were performed comparing the HNRNPU cohort to 56 previously reported DNAm episignatures.
RESULTS: A robust and reproducible DNAm episignature and global DNAm profile were identified. Correlation analysis identified partial overlap and similarity of the global HNRNPU DNAm profile to several other rare disorders.
CONCLUSION: This study demonstrates new evidence of a specific and sensitive DNAm episignature associated with pathogenic heterozygous HNRNPU-variants, establishing its utility as a clinical biomarker for the expansion of the EpiSignTM diagnostic test.
PMID:37120726 | DOI:10.1016/j.gim.2023.100871
