De novo missense variants in HECW2 are associated with neurodevelopmental delay and hypotonia

Academic Article

Abstract

  • Background The causes of intellectual disability (ID) are diverse and de novo mutations are increasingly recognised to account for a significant proportion of ID. Methods and results In this study, we performed whole exome sequencing on a large cohort of patients with ID or neurodevelopmental delay and identified four novel de novo predicted deleterious missense variants in HECW2 in six probands with ID/developmental delay and hypotonia. Other common features include seizures, strabismus, nystagmus, cortical visual impairment and dysmorphic facial features. HECW2 is an ubiquitin ligase that stabilises p73, a crucial mediator of neurodevelopment and neurogenesis. Conclusion This study implicates pathogenic genetic variants in HECW2 as potential causes of neurodevelopmental disorders in humans.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Berko ER; Cho MT; Eng C; Shao Y; Sweetser DA; Waxler J; Robin NH; Brewer F; Donkervoort S; Mohassel P
  • Start Page

  • 93
  • End Page

  • 99
  • Volume

  • 54
  • Issue

  • 2