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

J Med Genet. 2017 Feb;54(2):84-86. doi: 10.1136/jmedgenet-2016-103943. Epub 2016 Jul 7.

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.

Keywords: HECW2; de novo; intellectual disability; neurodevelopmental delay; whole exome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Exome / genetics
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Male
  • Muscle Hypotonia / genetics*
  • Muscle Hypotonia / pathology
  • Mutation, Missense / genetics
  • Neurodevelopmental Disorders / genetics*
  • Neurodevelopmental Disorders / pathology
  • Tumor Protein p73 / genetics*
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • Tumor Protein p73
  • p73 protein, human
  • HECW2 protein, human
  • Ubiquitin-Protein Ligases