Early infantile epileptic encephalopathy due to biallelic pathogenic variants in PIGQ: Report of seven new subjects and review of the literature

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


We investigated seven children from six families to expand the phenotypic spectrum associated with an early infantile epileptic encephalopathy caused by biallelic pathogenic variants in the phosphatidylinositol glycan anchor biosynthesis class Q (PIGQ) gene. The affected children were all identified by clinical or research exome sequencing. Clinical data, including EEGs and MRIs, was comprehensively reviewed and flow cytometry and transfection experiments were performed to investigate PIGQ function. Pathogenic biallelic PIGQ variants were associated with increased mortality. Epileptic seizures, axial hypotonia, developmental delay and multiple congenital anomalies were consistently observed. Seizure onset occurred between 2.5 months and 7 months of age and varied from treatable seizures to recurrent episodes of status epilepticus. Gastrointestinal issues were common and severe, two affected individuals had midgut volvulus requiring surgical correction. Cardiac anomalies including arrythmias were observed. Flow cytometry using granulocytes and fibroblasts from affected individuals showed reduced expression of glycosylphosphatidylinositol (GPI)-anchored proteins. Transfection of wildtype PIGQ cDNA into patient fibroblasts rescued this phenotype. We expand the phenotypic spectrum of PIGQ-related disease and provide the first functional evidence in human cells of defective GPI-anchoring due to pathogenic variants in PIGQ.


  • Devon L. Johnstone
  • Thi Tuyet Mai Nguyen
  • Jessica Zambonin
  • Kristin D. Kernohan
  • Anik St-Denis
  • Nissan V. Baratang
  • Taila Hartley
  • Michael T. Geraghty
  • Julie Richer
  • Jacek Majewski
  • Eric Bareke
  • Andrea Guerin
  • Manuela Pendziwiat
  • Loren D.M. Pena
  • Hilde M.H. Braakman
  • Karen W. Gripp
  • Andrew C. Edmondson
  • Miao He
  • Rebecca C. Spillmann
  • Erik A. Eklund
  • Och 4 andra
  • Allan Bayat
  • Hugh J. McMillan
  • Kym M. Boycott
  • Philippe M. Campeau
Enheter & grupper
Externa organisationer
  • Children's Hospital of Eastern Ontario
  • University of Montreal, Canada
  • McGill University
  • Queen's University
  • University of Kiel
  • Cincinnati Children's Hospital Medical Center
  • Maastricht University
  • Radboud University Medical Center
  • Nemours Alfred I. duPont Hospital for Children
  • The Children's Hospital of Philadelphia
  • Duke University Medical Center
  • Dianalund Epilepsy Hospital
  • University of Southern Denmark
  • Centre Hospitalier Universitaire Sainte-Justine
  • University of Cincinnati
  • Radboud University Nijmegen
  • Skåne University Hospital

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurovetenskaper


Sidor (från-till)1321-1332
Antal sidor12
TidskriftJournal of Inherited Metabolic Disease
Utgåva nummer6
Tidigt onlinedatum2020 jun 26
StatusPublished - 2020 nov
Peer review utfördJa