Dataset Information

Reduced cell surface levels of GPI-linked markers in a new case with PIGG loss of function.

ABSTRACT: Glycosylphosphatidylinositol (GPI) is a glycolipid that tethers more than 150 different proteins to the cell surface. Aberrations in biosynthesis of GPI anchors cause congenital disorders of glycosylation with clinical features including intellectual disability (ID), seizures, and facial dysmorphism. Here, we present two siblings with ID, cerebellar hypoplasia, cerebellar ataxia, early-onset seizures, and minor facial dysmorphology. Using exome sequencing, we identified a homozygous nonsense variant (NM_001127178.1:c.1640G>A, p.Trp547*) in the gene Phosphatidylinositol Glycan Anchor Biosynthesis, Class G (PIGG) in both the patients. Variants in several other GPI anchor synthesis genes lead to a reduced expression of GPI-anchored proteins (GPI-APs) that can be measured by flow cytometry. No significant differences in GPI-APs could be detected in patient granulocytes, consistent with recent findings. However, fibroblasts showed a reduced global level of GPI anchors and of specific GPI-linked markers. These findings suggest that fibroblasts might be more sensitive to pathogenic variants in GPI synthesis pathway and are well suited to screen for GPI-anchor deficiencies. Based on genetic and functional evidence, we confirm that pathogenic variants in PIGG cause an ID syndrome, and we find that loss of function of PIGG is associated with GPI deficiency.

SUBMITTER: Zhao JJ

PROVIDER: S-EPMC6180480 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Reduced cell surface levels of GPI-linked markers in a new case with PIGG loss of function.

Zhao Jin James JJ Halvardson Jonatan J Knaus Alexej A Georgii-Hemming Patrik P Baeck Peter P Krawitz Peter M PM Thuresson Ann-Charlotte AC Feuk Lars L

Human mutation 20170612 10

Glycosylphosphatidylinositol (GPI) is a glycolipid that tethers more than 150 different proteins to the cell surface. Aberrations in biosynthesis of GPI anchors cause congenital disorders of glycosylation with clinical features including intellectual disability (ID), seizures, and facial dysmorphism. Here, we present two siblings with ID, cerebellar hypoplasia, cerebellar ataxia, early-onset seizures, and minor facial dysmorphology. Using exome sequencing, we identified a homozygous nonsense var ...[more]

PMID: 28581210

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Reduced cell surface levels of GPI-linked markers in a new case with PIGG loss of function.

Publications

Reduced cell surface levels of GPI-linked markers in a new case with PIGG loss of function.

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