Ketogenic diet modifies ribosomal protein dysregulation in KMT2D Kabuki syndrome.

ABSTRACT:

Background

Kabuki syndrome (KS) is a genetic disorder caused by DNA mutations in KMT2D, a lysine methyltransferase that methylates histones and other proteins, and therefore modifies chromatin structure and subsequent gene expression. Ketones, derived from the ketogenic diet, are histone deacetylase inhibitors that can 'open' chromatin and encourage gene expression. Preclinical studies have shown that the ketogenic diet rescues hippocampal memory neurogenesis in mice with KS via the epigenetic effects of ketones.

Methods

Single-cell RNA sequencing and mass spectrometry-based proteomics were used to explore molecular mechanisms of disease in individuals with KS (n = 4) versus controls (n = 4).

Findings

Pathway enrichment analysis indicated that loss of function mutatio

SUBMITTER: Tsang E 

PROVIDER: S-EPMC11134553 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature