Null Mutation in PGAP1 Impairing Gpi-Anchor Maturation in Patients with Intellectual Disability and Encephalopathy

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Glycosylphosphatidylinositols (GPI) are glycolipid anchors that anchor various proteins to the cell surface. At least 26 genes are involved in biosynthesis and modification of the GPI anchors. Recently, mutations in eight of those genes have been described. Although those mutations do not fully abolish the functions of encoded enzymes, they lead to a decreased expression of surface GPI-anchored proteins and to different forms of intellectual disability. Here we report a mutation in PGAP1 that encodes a protein that modifies the GPI anchor. We found that the mutation leads to a full loss of PGAP1 enzyme activity, but that the patient cells still express normal levels of surface GPI-anchored proteins. However, the GPI anchors have an abnormal lipid structure that is resistant to cleavage by phosphatidylinositol-specific phospholipase C. Our results add PGAP1 to the growing list of GPI abnormalities that cause intellectual disability and indicate that the fine structure of GPI-anchors is also important for a normal neurological development.

Vyšlo v časopise: Null Mutation in PGAP1 Impairing Gpi-Anchor Maturation in Patients with Intellectual Disability and Encephalopathy. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004320
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004320

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