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

Autor:	Johnstone DL; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada., Nguyen TTM; Research Center, CHU Sainte Justine, University of Montreal, Montreal, Quebec, Canada., Zambonin J; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.; Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada., Kernohan KD; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.; Division of Metabolics and Newborn Screening, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada., St-Denis A; Research Center, CHU Sainte Justine, University of Montreal, Montreal, Quebec, Canada., Baratang NV; Research Center, CHU Sainte Justine, University of Montreal, Montreal, Quebec, Canada., Hartley T; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada., Geraghty MT; Division of Metabolics and Newborn Screening, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada., Richer J; Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada., Majewski J; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.; McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada., Bareke E; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.; McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada., Guerin A; Division of Medical Genetics, Department of Pediatrics, Queen's University, Kingston, Ontario, Canada., Pendziwiat M; Department of Neuropediatrics, Christian-Albrechts-University of Kiel, Kiel, Germany., Pena LDM; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Braakman HMH; Department of Neurology, Academic Center for Epileptology Kempenhaeghe & Maastricht University Medical Center, Heeze, The Netherlands.; Department of Pediatric Neurology, Amalia Children's Hospital, Radboud University Medical Center & Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands., Gripp KW; Division of Medical Genetics, A. I. DuPont Hospital for Children/Nemours, Wilmington, Delaware, USA., Edmondson AC; Department of Pediatrics, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., He M; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Spillmann RC; Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA., Eklund EA; Department of Pediatric Neurology, Region Skåne and Clinical Sciences, Lund University Skåne University Hospital (SUS), Lund, Sweden., Bayat A; Department of Genetics and Personalized Medicine, Danish Epilepsy Centre, Dianalund, Denmark.; Institute for Regional Health Services Research, University of Southern Denmark, Odense, Denmark., McMillan HJ; Division of Neurology, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada., Boycott KM; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.; Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada., Campeau PM; Research Center, CHU Sainte Justine, University of Montreal, Montreal, Quebec, Canada.; Department of Pediatrics, Sainte-Justine Hospital, University of Montreal, Montreal, Quebec, Canada.
Jazyk:	angličtina
Zdroj:	Journal of inherited metabolic disease [J Inherit Metab Dis] 2020 Nov; Vol. 43 (6), pp. 1321-1332. Date of Electronic Publication: 2020 Aug 03.
DOI:	10.1002/jimd.12278
Abstrakt:	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. (© 2020 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)
Databáze:	MEDLINE
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