Mutations in PIGU Impair the Function of the GPI Transamidase Complex, Causing Severe Intellectual Disability, Epilepsy, and Brain Anomalies

The glycosylphosphatidylinositol (GPI) anchor links over 150 proteins to the cell surface and is present on every cell type. Many of these proteins play crucial roles in neuronal development and function. Mutations in 18 of the 29 genes implicated in the biosynthesis of the GPI anchor have been identified as the cause of GPI biosynthesis deficiencies (GPIBDs) in humans. GPIBDs are associated with intellectual disability and seizures as their cardinal features. An essential component of the GPI transamidase complex is PIGU, along with PIGK, PIGS, PIGT, and GPAA1, all of which link GPI-anchored proteins (GPI-APs) onto the GPI anchor in the endoplasmic reticulum (ER).

Source: The American Journal of Human Genetics - July 24, 2019 Category: Genetics & Stem Cells Authors: Alexej Knaus, Fanny Kort üm, Tjitske Kleefstra, Asbjørg Stray-Pedersen, Dejan Đukić, Yoshiko Murakami, Thorsten Gerstner, Hans van Bokhoven, Zafar Iqbal, Denise Horn, Taroh Kinoshita, Maja Hempel, Peter M. Krawitz Tags: Report Source Type: research