Glycosylphosphatidylinositol (GPI) anchor deficiency caused by mutations inPIGWis associated with West syndrome and hyperphosphatasia with mental retardation syndrome
- 23 December 2013
- journal article
- case report
- Published by BMJ in Journal of Medical Genetics
- Vol. 51 (3), 203-207
- https://doi.org/10.1136/jmedgenet-2013-102156
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.Keywords
This publication has 19 references indexed in Scilit:
- A novel intellectual disability syndrome caused by GPI anchor deficiency due to homozygous mutations inPIGTJournal of Medical Genetics, 2013
- PGAP2 Mutations, Affecting the GPI-Anchor-Synthesis Pathway, Cause Hyperphosphatasia with Mental Retardation SyndromeAmerican Journal of Human Genetics, 2013
- Mutations in PIGO, a Member of the GPI-Anchor-Synthesis Pathway, Cause Hyperphosphatasia with Mental RetardationAmerican Journal of Human Genetics, 2012
- Mutations in the Glycosylphosphatidylinositol Gene PIGL Cause CHIME SyndromeAmerican Journal of Human Genetics, 2012
- The Phenotype of a Germline Mutation in PIGA: The Gene Somatically Mutated in Paroxysmal Nocturnal HemoglobinuriaAmerican Journal of Human Genetics, 2012
- Multiple congenital anomalies-hypotonia-seizures syndrome is caused by a mutation in PIGNJournal of Medical Genetics, 2011
- Identity-by-descent filtering of exome sequence data identifies PIGV mutations in hyperphosphatasia mental retardation syndromeNature Genetics, 2010
- Biosynthesis, Remodelling and Functions of Mammalian GPI-anchored Proteins: Recent ProgressThe Journal of Biochemistry, 2008
- Hypomorphic promoter mutation in PIGM causes inherited glycosylphosphatidylinositol deficiencyNature Medicine, 2006
- PIG-M transfers the first mannose to glycosylphosphatidylinositol on the lumenal side of the ERThe EMBO Journal, 2001