A novel de novo AP2M1 variant in a patient with attention-deficit/hyperactivity disorder, oppositional defiant disorder, and unexpected hemiplegic migraine

Abstract

The adaptor-related protein AP2 is a heterotetrameric complex consisting of α, β, μ, and σ subunits, which plays a crucial role in clathrin-mediated endocytosis (CME) and especially in the retrieval of synaptic vesicles at nerve terminals. 1 Interestingly, several stud- ies have elucidated that CME of plasma membrane proteins con- trols the neuronal surface expression of γ- aminobutyric acid and glutamate receptors involved in long-term plastic changes in neuro- transmission and excitatory/inhibitory balance.1 However, only five individuals with AP2M1 mutations associated with neurodevelop - mental disorders have been reported in the literature so far, 1,2 and the few clinical data available suggest that AP2M1 mutations cause a variable phenotype ranging from severe intellectual disability, autism spectrum disorder, and epilepsy to isolated global develop - mental delay (GDD). We report an individual carrying a novel de novo AP2M1 variant with attention- deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, and unexpected hemiplegic migraine (HM).