A novel homozygous variant of the PIGK gene caused by paternal disomy in a patient with neurodevelopmental disorder, cerebellar atrophy, and seizures

Glycosylphosphatidylinositol (GPI)-anchored proteins are located at the cell surface by a covalent attachment between protein and GPI embedded in the plasma membrane. This attachment is catalyzed by GPI transamidase comprising five subunits (PIGK, PIGS, PIGT, PIGU, and GPAA1) in the endoplasmic reticulum. Loss of either subunit of GPI transamidase eliminates cell surface localization of GPI-anchored proteins. In humans, pathogenic variants in either subunit of GPI transamidase cause neurodevelopmental disorders. However, how the loss of GPI-anchored proteins triggers neurodevelopmental defects remains largely unclear. Here, we identified a novel homozygous variant of PIGK, NM_005482:c.481A > G,p. (Met161Val), in a Japanese female patient with neurodevelopmental delay, hypotonia, cerebellar atrophy, febrile seizures, hearing loss, growth impairment, dysmorphic facial features, and brachydactyly.