A novel PIGA mutation in a family with X-linked, early-onset epileptic encephalopathy

Brain Dev. 2016 Sep;38(8):750-4. doi: 10.1016/j.braindev.2016.02.008. Epub 2016 Feb 26.

Abstract

Early-onset epileptic encephalopathies (EOEEs) are severe and intractable infantile-onset epilepsies with progressive intellectual disability and other associated neurologic comorbidities. Whole-exome sequencing (WES) was recently used to determine the causative gene mutations in individuals with unclassified EOEEs. The present study used WES to determine the causative variant in a family with X-linked, EOEE. One potential variant (c. 427A>G, NM_002641.3; p.Lys143Glu, NP_002632.1) of the gene encoding phosphatidylinositol glycan biosynthesis class A protein (PIGA; PIGA) was found, which was verified by Sanger sequencing. The functional effect of this PIGA mutation was assessed by the surface expression levels of glycosylphosphatidylinositol-anchored proteins on blood cells: CD16 on red blood cells was significantly decreased in the proband (by 11.0%) and his mother (by 15.6%). This is the second report of a less-severe form of PIGA deficiency.

Keywords: Epileptic encephalopathy; Focal seizure; Genetics; Infant; PIGA.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Epilepsies, Myoclonic / genetics
  • Family
  • Fatal Outcome
  • GPI-Linked Proteins / blood
  • Genotyping Techniques
  • Humans
  • Infant
  • Male
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics*
  • Mutation*
  • Pedigree
  • Receptors, IgG / blood
  • Spasms, Infantile / blood
  • Spasms, Infantile / genetics*
  • Spasms, Infantile / therapy

Substances

  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Membrane Proteins
  • Receptors, IgG
  • phosphatidylinositol glycan-class A protein

Supplementary concepts

  • Infantile Epileptic-Dyskinetic Encephalopathy