Missense variant in <scp><i>PIGM</i></scp> associated with severe cystic encephalomalacia and portal vein thrombosis: Phenotypic and genotypic expansion of the glycosylphosphatidylinositol biosynthesis defect‐1 (<scp>GPIBD1</scp>)

AbstractGlycosylphosphatidylinositols (GPIs) are a type of glycolipid responsible for anchoring many important proteins to the cell membrane surface. Defects in the synthesis of GPIs can lead to a group of multisystem disorders known as the inherited GPI deficiencies (IGDs). Homozygosity for the c.‐270C > G variant in the promoter of PIGM has been associated with a IGD subtype known as glycosylphosphatidylinositol biosynthesis defect‐1 (GPIBD1). The several cases reported in the literature have been described to have a milder neurologic phenotype in comparison to the other IGDs and have been treated with sodium phenylbutyrate with some degree of success. These patients typically present with portal and hepatic vein thrombosis and mostly develop absence seizures. Here we describe a patient homozygous for a nonsynonymous variant in PIGM who deceased at 9 weeks of life and had multiple physical dysmorphisms (rocker bottom feet, midline cleft palate, thickened and lichenified skin), portal vein thrombosis, CNS structural anomalies (progressive multicystic encephalomalacia and ventriculomegaly), and a neurological phenotype of a diffuse encephalopathy. This is the first known case report of a PIGM‐related IGD/CDG due to a coding variant.

Missense variant in PIGM associated with severe cystic encephalomalacia and portal vein thrombosis: Phenotypic and genotypic expansion of the glycosylphosphatidylinositol biosynthesis defect‐1 (GPIBD1) Journal Articles