De novo variants in AGO1 recapitulate a heterogeneous neurodevelopmental disorder phenotype.

ABSTRACT

AGO1, as one of the rare genes in neurodevelopmental disorders, is involved in the microRNA-induced silencing complex. Here, we describe the clinical and genetic features of 18 individuals with de novo AGO1 variants four new and 14 previously reported. Three variants are identified two in-frame deletion variants and one missense variant. The spectrum of AGO1-related disorders included global development delay (GDD), intellectual disability (ID) with or without epilepsy, autism spectrum disorder, hypotonia and dysmorphisms. Focal seizures are the most common type of seizure, occasionally with atypical absence. Mild deafness may be a new phenotype of AGO1-releated disease. Gly199Ser may be a hot-spot variant of AGO1 with the same phenotype GDD/ID, intractable epilepsy, remarkably with Rolandic discharges, and even reaching electrical status epilepticus during sleep.