Submission Details

Autosomal dominant

10/07/2019

The PIGU gene is located on chromosome 20 at 20q11.22 and encodes the phosphatidylinositol glycan anchor biosynthesis class U protein, a ubiquitously expressed protein which is a component of the glycosylphosphatidylinositol (GPI) transamidase complex. The glycosylphosphatidylinositol (GPI) anchor links many types of protein to the cell surface and the GPI transamidase complex couples the GPI anchored proteins (GPI-APs) onto the GPI anchor within the endoplasmic reticulum before transport to the cell surface. GPI-APs mediate a range of cellular processes including cellular signalling, cell adhesion and immune modulation as well as playing key roles in embryogenesis and neurodevelopment. The PIGU gene was first reported in relation to autosomal dominant PIGU-related glycosylphosphatidylinositol biosynthesis deficiency in 2019 (31353022: Knaus et al. 2019). In this report, two missense variants were associated with PIGU-related glycosylphosphatidylinositol biosynthesis deficiency in five individuals from three families. In all cases variants were identified in a homozygous state and caused a reduction in presentation of cell surface GPI anchored proteins, due to decreased GPI transaminase activity (31353022: Knaus et al. 2019). A number of genes associated with biosynthesis of the GPI anchor have been identified, these disorders, collectively known as GPI biosynthesis deficiencies are associated with a clinical spectrum of disease which includes intellectual disability and seizures as the key features (30054924: Bellai-Dussault et al. 2019). Specifically, three further components of the GPI transamidase complex; GPAA1, PIGT and PIGS have all been associated with autosomal recessive glycosylphosphatidylinositol biosynthesis deficiencies (12802054: Hong et al. 2013). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship.

31353022 12802054 30054924