A novel TUBB3 mutation in a sporadic patient with asymmetric cortical dysplasia

Am J Med Genet A. 2016 Apr;170A(4):1076-9. doi: 10.1002/ajmg.a.37545. Epub 2016 Jan 6.

Abstract

Recent advances in molecular technology have led to the discovery of several genes related to human malformations of cortical development (MCDs). The beta-tubulin class III gene (TUBB3) was identified as a gene responsible for MCDs. Although mouse-model experiments have not revealed any findings of neuronal migration disorders, human TUBB3 mutations have been identified in patients with congenital fibrosis of the extraocular muscles. Since the discovery of a TUBB3 mutation, only 15 mutations have been identified. In this study, comprehensive mutation screening through next-generation sequencing identified a novel TUBB3 mutation (p.Ser230Leu) in a sporadic patient with moderate developmental delay associated with mild MCD. Compared to patients with the alpha-tubulin class 1a gene (TUBA1A) mutations, patients with TUBB3 mutations show milder phenotypic manifestations and milder MCD. Therefore, patients with milder MCD manifestations may be under-diagnosed, and TUBB3 mutations may be rarely identified. Additional genotype-phenotype information should be accumulated for further understanding of the TUBB3 functional relevance.

Keywords: beta-tubulin class III (TUBB3); malformation of cortical development (MCD); mutation; tubulin family.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / pathology
  • Comparative Genomic Hybridization
  • DNA Mutational Analysis
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / genetics
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Malformations of Cortical Development / diagnosis*
  • Malformations of Cortical Development / genetics*
  • Mutation*
  • Pedigree
  • Phenotype*
  • Tubulin / genetics*

Substances

  • TUBB3 protein, human
  • Tubulin