DNA methylation episignature and comparative epigenomic profiling of HNRNPU-related neurodevelopmental disorder.
Genet Med
; 25(8): 100871, 2023 08.
Article
em En
| MEDLINE
| ID: mdl-37120726
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 multicenter collaboration, were assessed using Infinium Methylation EPIC arrays. Statistical and functional correlation analyses were performed comparing the HNRNPU cohort with 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 EpiSign diagnostic test.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metilação de DNA
/
Transtornos do Neurodesenvolvimento
Tipo de estudo:
Clinical_trials
Limite:
Humans
Idioma:
En
Revista:
Genet Med
Ano de publicação:
2023
Tipo de documento:
Article