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

Background

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.

Case presentation

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

Conclusions

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.