Association of HECW2 variants with developmental and epileptic encephalopathy and knockdown of zebrafish hecw2a

Am J Med Genet A. 2021 Feb;185(2):377-383. doi: 10.1002/ajmg.a.61958. Epub 2020 Nov 18.

Abstract

Developmental and epileptic encephalopathy (DEE) is a severe encephalopathy in infants and early childhood. In this study we reported a recurrent de novo variant (c.3985C>T, p.R1330W) in HECW2 (HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2) (MIM# 617245) identified by screening 240 patients with DEE and summarized clinical features of published DEE patients with HECW2 variants. Functionally, transcriptional knockdown of zebrafish hecw2a led to early morphological abnormalities in the brain tissues. These results suggest a potential functional link between HECW2 dysfunction and brain development.

Keywords: HECW2; developmental encephalopathy; epilepsy; zebrafish model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Brain Diseases / epidemiology
  • Brain Diseases / genetics*
  • Brain Diseases / pathology
  • Child
  • Child, Preschool
  • Disease Models, Animal
  • Exome Sequencing
  • Genetic Predisposition to Disease
  • Humans
  • Infant
  • Intellectual Disability / epidemiology
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Male
  • Mutation / genetics
  • Ubiquitin-Protein Ligases / genetics*
  • Zebrafish / genetics
  • Zebrafish Proteins / genetics*

Substances

  • Zebrafish Proteins
  • HECW2 protein, human
  • Ubiquitin-Protein Ligases