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Glycosylphosphatidylinositol (GPI) anchor deficiency caused by mutations in PIGW is associated with West syndrome and hyperphosphatasia with mental retardation syndrome
  1. Tomohiro Chiyonobu1,
  2. Norimitsu Inoue2,
  3. Masafumi Morimoto1,
  4. Taroh Kinoshita3,4,
  5. Yoshiko Murakami3,4
  1. 1Department of Pediatrics, Kyoto Prefectural University of Medicine, Kamigyo, Kyoto, Japan
  2. 2Department of Molecular Genetics, Osaka Medical Center for Cancer, Osaka, Japan
  3. 3Department of Immunoregulation, Research Institute for Microbial Diseases, Suita, Osaka, Japan
  4. 4Laboratory of Immunoglycobiology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan
  1. Correspondence to Dr Yoshiko Murakami, Department of Immunoregulation Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan; yoshiko{at}biken.osaka-u.ac.jp

Abstract

Background Glycosylphosphatidylinositol (GPI) is a glycolipid that anchors 150 or more kinds of proteins to the human cell surface. There are at least 26 genes involved in the biosynthesis and remodelling of GPI anchored proteins (GPI-APs). Recently, inherited GPI deficiencies (IGDs) were reported which cause intellectual disability often accompanied by epilepsy, coarse facial features and multiple anomalies that vary in severity depending upon the degree of defect and/or step in the pathway of affected gene.

Methods and Results A patient born to non-consanguineous parents developed intractable seizures with typical hypsarrhythmic pattern in electroencephalography, and was diagnosed as having West syndrome. Because the patient showed severe developmental delay with dysmorphic facial features and hyperphosphatasia, characteristics often seen in IGDs, the patient was tested for GPI deficiency. The patient had decreased surface expression of GPI-APs on blood granulocytes and was identified to be compound heterozygous for NM_178517:c.211A>C and c.499A>G mutations in PIGW by targeted sequencing.

Conclusion Here we describe the first patient with deficiency of PIGW, which is involved in the addition of the acyl-chain to inositol in an early step of GPI biosynthesis. Therefore, IGD should be considered in West syndrome and flow cytometric analysis of blood cells is effective in screening IGD.

  • Epilepsy and seizures
  • Clinical genetics
  • Neurology

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