A novel stop-gain CUL3 mutation in a Japanese patient with autism spectrum disorder

Brain Dev. 2021 Feb;43(2):303-307. doi: 10.1016/j.braindev.2020.09.015. Epub 2020 Oct 21.

Abstract

Background: CUL3 encodes cullin-3, a core component of a ubiquitin E3 ligase. CUL3 mutations have recently been associated with autism spectrum disorder (ASD); however, the detailed clinical courses have been described in only a limited number of patients with CUL3 mutations and neurodevelopmental diseases, including ASD.

Case report: A 21-month-old Japanese girl presented with febrile status epilepticus and thereafter exhibited developmental regression, including loss of her verbal ability, eye contact, and skills in activities of daily living. Trio-based exome sequencing identified a de novo two-base insertion in CUL3, c.1758_1759insTG, p.(Thr587*).

Conclusion: We report a case of a patient with ASD and a stop-gain CUL3 variant. Screening of CUL3 variants is worth considering for patients with ASD, especially those with Rett-like developmental regression.

Keywords: Autism spectrum disorder; CUL3; Whole-exome sequencing.

Publication types

  • Case Reports

MeSH terms

  • Autism Spectrum Disorder / genetics*
  • Codon, Nonsense / genetics
  • Cullin Proteins / genetics*
  • Cullin Proteins / metabolism
  • Exome Sequencing / methods
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Infant
  • Japan
  • Mutation / genetics
  • Pedigree

Substances

  • CUL3 protein, human
  • Codon, Nonsense
  • Cullin Proteins