Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

The role of action representations in visual object recognition

It is typically assumed that perception for action and object recognition are subserved by functionally and neuroanatomically distinct processing streams in the brain. However, recent evidence challenges this classical view and suggests an interaction between both visual processing streams. While previous studies showed an influence of object perception on action-related tasks, we investigated whether action representations facilitate visual object recognition. In order to address this question, two briefly displayed masked objects were sequentially presented, either affording congruent or incongruent motor interactions. We found superior naming accuracy for object pairs with congruent as compared to incongruent motor interactions (Experiment 1). This action priming effect indicates that action representations can facilitate object recognition. We further investigated the nature of the representations underlying this action priming effect. The effect was absent when the prime stimulus was presented as a word (Experiment 2). Thus, the action priming effect seems to rely on action representations specified by visual object information. Our findings suggest that processes of object-directed action influence object recognition