Loss-of-function in RBBP5 results in a syndromic neurodevelopmental disorder associated with microcephaly.

ABSTRACT:

Purpose

Epigenetic dysregulation has been associated with many inherited disorders. RBBP5 (HGNC:9888) encodes a core member of the protein complex that methylates histone 3 lysine-4 and has not been implicated in human disease.

Methods

We identify 5 unrelated individuals with de novo heterozygous variants in RBBP5. Three nonsense/frameshift and 2 missense variants were identified in probands with neurodevelopmental symptoms, including global developmental delay, intellectual disability, microcephaly, and short stature. Here, we investigate the pathogenicity of the variants through protein structural analysis and transgenic Drosophila models.

Results

Both missense p.(T232I) and p.(E296D) variants affect evolutionarily conserved amino acids located at the interface betw

SUBMITTER: Huang Y 

PROVIDER: S-EPMC11648989 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature