A novel intellectual disability syndrome caused by GPI anchor deficiency due to homozygous mutations inPIGT

Abstract

We identified mutations in PIGT as the cause of a novel autosomal recessive intellectual disability syndrome. Our results demonstrate a new pathogenic mechanism in the GPI anchor pathway and expand the clinical spectrum of disorders belonging to the group of GPI anchor deficiencies.

Novel genetic causes for cerebral visual impairment

“…The third glycosylation gene in which a variant was identified, PGAP1 (patient 12, reported elsewhere), is important in the GPI-anchor synthesis pathway. 26 Several other genes, PIGA, PIGN, and PIGT, implicated in this pathway are known to be implicated in CVI and ID as well, 29,[37][38][39][40] and recently, also PGAP1 variants were found to be associated with CVI and ID. 29,41 RERE is another gene with a functional link with a gene known to be aberrant in CVI.…”

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).…”

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

“…The product of this gene encodes a protein for the biosynthesis of the GPI anchors in the attachment of proteins to the plasma membrane during normal development. 6,7 More than 150 proteins and 13 different genes have heterogeneous functions in a multistep process that produce GPI-protein complex. Syndrome (FCCS) and a less-severe form of encephalopathy.…”