de novo KDM5B Mutation in a Patient with Autism Spectrum Disorder and Obsessive-Compulsive Disorder: Case Report

The KDM5B gene encodes a lysine histone demethylase that is essential in epigenetic regulation and human development. Homozygous and compound heterozygous variants of KDM5B have been associated with a distinct syndrome characterized by developmental delay, intellectual disability, and dysmorphic features. However, phenotypic presentations associated with heterozygous (HET) protein-truncating variants (PTVs) have been inconsistent, ranging from moderate to severe autism spectrum disorder (ASD) and intellectual disability (ID), to some individuals being unaffected with ASD or ID.

We report a de novo HET PTV (NM_006618.5 c.1708 C>T; p.R570X) in KDM5B in an 18-year-old Caucasian female patient, who presented with ASD, and then developed severe obsessive-compulsive disorder (OCD) and leading to depression and emotion dysregulation.

This case suggests a potential role for HET PTVs in the KDM5B gene in OCD pathogenesis and marks the first report of co-occurring ASD and OCD associated with a KDM5B variant.