A de novo missense variant in the DNM1 gene was identified in an ASD proband from the SPARK proband (Feliciano et al., 2019), while a damaging missense variant in this gene was identified in three ASD-affected siblings from the BARAKA-Qatar study and their father, who was diagnosed with ADHD and presented with autistic features (Abdi et al., 2023). Additional loss-of-function and damaging missense variants in DNM1 were reported in individuals from ASD and developmental delay cohorts in Wang et al., 2020. One of the five individuals with DNM1-related autosomal dominant developmental and epileptic encephalopathy described in EuroEPINOMICS-RES Consortium 2014 was reported to have autism spectrum disorder, while both individuals with DNM1-related autosomal recessive developmental and epileptic encephalopathy described in Yigit et al., 2022 were reported to present with stereotypical movements. A de novo missense variant in DNM1 was identified in twin siblings presenting with diagnoses of autism spectrum disorder, developmental delay, and intellectual disability without epileptic encephalopathy in Brereton et al., 2018, while a de novo missense variant in this gene was reported in a adult male with autism, intellectual disability, and mild epilepsy in Mei et al., 2023.
Molecular Function
This gene encodes a member of the dynamin subfamily of GTP-binding proteins. The encoded protein possesses unique mechanochemical properties used to tubulate and sever membranes, and is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Actin and other cytoskeletal proteins act as binding partners for the encoded protein, which can also self-assemble leading to stimulation of GTPase activity. Heterozygous and homozygous mutations in this gene are responsible for autosomal dominant and autosomal recessive forms of developmental and epileptic encephalopathy, respectively (EuroEPINOMICS-RES Consortium 2014; Deciphering Developmental Disorders Study 2015; Yigit et al., 2022; AlTassan et al., 2022).
