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

Area of Science:

• Genetics
• Neuroscience
• Epigenetics

Background:

• The KDM5B gene is crucial for epigenetic regulation and human development, encoding a lysine histone demethylase.
• Disorders linked to KDM5B variants include developmental delay, intellectual disability, and dysmorphic features.
• Phenotypic variability exists for heterozygous (HET) protein-truncating variants (PTVs) of KDM5B, ranging from unaffected to severe autism spectrum disorder (ASD) and intellectual disability (ID).

Observation:

• A case study of an 18-year-old female with a de novo HET PTV in KDM5B (NM_006618.5:c.1708C>T; p.R570X) is presented.
• The patient initially presented with ASD.
• Subsequently, she developed severe obsessive-compulsive disorder (OCD), depression, and emotion dysregulation.

Findings:

• This report details the first instance of co-occurring ASD and OCD associated with a KDM5B variant.
• The findings suggest a potential role for HET PTVs in KDM5B in the pathogenesis of OCD.

Implications:

• This case expands the known phenotypic spectrum associated with KDM5B HET PTVs.
• Further research into KDM5B's role in neurodevelopmental disorders, particularly OCD, is warranted.
• Understanding KDM5B's function may offer new therapeutic targets for related conditions.