Recurrent de novo pathogenic variant of WASF1 in a Japanese patient with neurodevelopmental disorder with absent language and variable seizures

Abstract

A recurrent de novo pathogenic variant of WASF1, NM_003931:c.1516C>T [p.Arg506*], was identified in a 6-year-old female Japanese patient with severe developmental delay, hypotonia, hyperkinetic behavior, and distinctive facial features. The initial report of five adult patients with WASF1 variants was the only previous report regarding variants of this gene; this is the second such report, reaffirming that rare but recurrent truncating variants of WASF1 are associated with severe neurodevelopmental disorders.

Orchestration of synaptic functions by WAVE regulatory complex-mediated actin reorganization

“…Exome sequencing and whole-genome sequencing have also identified a number of de novo truncating or missense variants of WAVE1 in patients with various neurodevelopmental symptoms 137 – 140 . Certain WAVE1 variants were predicted to disrupt the WCA domain 11 .…”

The intrinsically disordered cytoplasmic tail of a dendrite branching receptor uses two distinct mechanisms to regulate the actin cytoskeleton

“…Disruption of WRC function can profoundly affect the nervous system in animals, resulting in altered spine morphology and density, intellectual disability, and embryonic death ( Dahl et al, 2003 ; Soderling et al, 2003 ). Mutations in WAVE and other WRC subunits have been linked to various neurodevelopmental disorders in humans, including neurodevelopmental disorder with absent language and variable seizures, developmental and epileptic encephalopathy-65, and Alzheimer’s disease ( Begemann et al, 2021 ; Conway et al, 2018 ; Ito et al, 2018 ; Kirkpatrick et al, 2017 ; Kramer et al, 2022 ; Kumar et al, 2013 ; Olive et al, 2020 ; Rottner et al, 2021 ; Shimojima Yamamoto et al, 2021 ; Sims et al, 2017 ; Srivastava et al, 2021 ; Zhao et al, 2021 ; Zweier et al, 2019 ).…”

The recurrent WASF1 nonsense variant identified in two unaffected Chinese families with neurodevelopmental disorder: case report and review of the literatures

“…Neurodevelopmental disorder with absent language and variable seizures (NEDALVS, # 618707) is an autosomal dominant disorder of neurodevelopment, which has clinical heterogeneity [ 1 ]. The phenotype of NEDALVS involves multiple organs and body parts [ 2 ]. Nervous system phenotypes include intellectual impairment, motor developmental delay, unsteady gait, language deficits, autistic features, and seizures.…”