PIGA mutations cause early-onset epileptic encephalopathies and distinctive features

Abstract

Our study confirmed that PIGA mutations are one genetic cause of EOEE, suggesting that GPI-anchor deficiencies may be an underlying cause of EOEE.

A Neonate with aPIGAc.1234C>T Mutation as a Novel Cause of Neonatal Early Infantile Epileptic Encephalopathy

“…We could not do exome sequencing analysis with patient's mother because of her refusal. The clinical characteristics of our case were very similar to those reported previously by Kato et al 11 The phenotype of our case could be classified into severe PIGA deficiency in cluding refractory epileptiform discharges with a burstsuppression pattern on EEG, dysmorphic features and anomalies of other organs. 12 Our case showed no anemia or paroxysmal nocturnal hemoglobinuria that is caused by somatic PIGA mutations.…”

Glycosylphosphatidylinositol Anchor Modification Machinery Deficiency Is Responsible for the Formation of Pro-Prion Protein (PrP) in BxPC-3 Protein and Increases Cancer Cell Motility

“…More than 20 genes are known to be important in the synthesis, assembly of the GPI anchor components, cleavage of the GPI-PSS, and eventual en bloc attachment of an assembled GPI anchor to its substrate (21). Mutations in GPI anchor synthesis enzymes are associated with many human diseases; most of these diseases affect neuronal development (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). Furthermore, a lack of GPI anchored protein in cancer cells has also been reported to be due to transcriptional silencing of the genes involved in biosynthesis of the GPI anchor (36).…”

Mutations in the phosphatidylinositol glycan C (PIGC) gene are associated with epilepsy and intellectual disability

“…Most had their onset in early childhood and were manifesting by neurodevelopmental disorders, epilepsy and ID. Nonetheless, wide phenotypic spectrum is evident even within the GlcNAc transferase complex; PIGA somatic mutations cause paroxysmal nocturnal haemoglobinuria16 while the clinical phenotype of germline PIGA mutations ranges from severe, often lethal, epileptic encephalopathy of infancy associated with dysmorphic face, to ID and treatable seizures without facial dysmorphism 17. Mutations in PIGQ were reported in an individual with early onset epilepsy18 and PIGY mutations were found in individuals with multisystem, lethal disease including dysmorphism, seizures, severe developmental delay, cataracts and early death 19.…”