Biallelic mutations in PIGP cause developmental and epileptic encephalopathy

Ann Clin Transl Neurol. 2019 Apr 11;6(5):968-973. doi: 10.1002/acn3.768. eCollection 2019 May.

Abstract

Developmental and epileptic encephalopathies are characterized by infantile seizures and psychomotor delay. Glycosylphosphatidylinositol biosynthesis defects, resulting in impaired tethering of various proteins to the cell surface, represent the underlying pathology in some patients. One of the genes involved, PIGP, has recently been associated with infantile seizures and developmental delay in two siblings. Here, we report the second family with a markedly overlapping phenotype due to a homozygous frameshift mutation (c.456delA;p.Glu153Asnfs*34) in PIGP. Flow cytometry of patient granulocytes confirmed reduced expression of glycosylphosphatidylinositol-anchored proteins as functional consequence. Our findings corroborate PIGP as a monogenic disease gene for developmental and epileptic encephalopathy.

MeSH terms

  • Brain / diagnostic imaging
  • Brain / physiology
  • Electroencephalography
  • Female
  • Glycosylphosphatidylinositols / genetics
  • Hexosyltransferases / chemistry
  • Hexosyltransferases / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Magnetic Resonance Imaging
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Mutation
  • Spasms, Infantile / genetics*
  • Spasms, Infantile / physiopathology*

Substances

  • Glycosylphosphatidylinositols
  • Membrane Proteins
  • Hexosyltransferases
  • PIGP protein, human

Supplementary concepts

  • Infantile Epileptic-Dyskinetic Encephalopathy

Grant support

This work was funded by German Research Foundation/Deutsche Forschungsgemeinschaft grant 1731/2‐1; Elterninitiative Kinderkrebsklinik e.V. grant 701900167.