Familial pachygyria in both genders related to a DCX mutation

Brain Dev. 2016 Jun;38(6):585-9. doi: 10.1016/j.braindev.2015.12.005. Epub 2015 Dec 29.

Abstract

Doublecortin (DCX) and tubulin play critical roles in neuronal migration. DCX mutations usually cause anterior dominant lissencephaly in males and subcortical band heterotopia (SBH) in females. We used whole-exome sequencing to investigate causative gene variants in a large family with late-childhood-onset focal epilepsy and anterior dominant pachygyria without SBH in both genders. Two potential variants were found for the genes encoding DCX and beta tubulin isotype 1 (TUBB1). The novel DCX mutation (p.D90G, NP_000546.2) appeared to be a major causative variant, whereas the novel mutation of TUBB1 (p.R62fsX, NP_110400.1) was found only in patients with more-severe intellectual disability after gender matching. We report an unusual DCX-related disorder exhibiting familial pachygyria without SBH in both genders.

Keywords: DCX; Focal seizures; Genetics; Intellectual disability; Pachygyria.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Child
  • DNA Mutational Analysis
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Epilepsies, Partial / genetics
  • Epilepsies, Partial / physiopathology
  • Family Health
  • Female
  • Humans
  • Intellectual Disability / genetics
  • Intellectual Disability / physiopathology
  • Lissencephaly / genetics*
  • Lissencephaly / physiopathology
  • Male
  • Microtubule-Associated Proteins / genetics*
  • Middle Aged
  • Mutation*
  • Neuropeptides / genetics*
  • Pedigree
  • Severity of Illness Index
  • Tubulin / genetics
  • Young Adult

Substances

  • DCX protein, human
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Microtubule-Associated Proteins
  • Neuropeptides
  • TUBB1 protein, human
  • Tubulin