Homozygous PIGT Mutation Lead to Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3

Abstract

PIGT encodes a subunit of the glycosylphosphatidylinositol transamidase complex, which catalyzes the attachment of proteins to GPI-anchors. A homozygous PIGT variant c.550G>A (p. E184K) in a Chinese boy with multiple malformations, hypotonia, seizure and profound development delay was identified by panel sequencing. Pathogenicity of the variant was confirmed by flow cytometry. The expression of CD16 and CD24 of this proband reduced to 16.92 and 22.16% compare with normal control respectively while which of his parents and sister were normal. This mutation raised the mRNA level on the peripheral blood mono nuclear cells of this patient. This study expanded the variant spectrum of MCAHS3, and CD16 could be an effective marker to evaluate the pathogenicity of PIGT mutation.

Complement and inflammasome overactivation mediates paroxysmal nocturnal hemoglobinuria with autoinflammation

“…Patients with PIGT-PNH had a germline heterozygous mutation in the PIGT gene in combination with somatic deletion of the normal PIGT gene. Germline PIGT mutations were reported in patients with inherited GPI deficiency (IGD) (Supplemental Table 2), which is characterized by developmental delay, seizures, hypotonia, and typical facial dysmorphism (11,(33)(34)(35)(36)(37)(38)(39). Inflammatory symptoms and intravascular hemolysis were not reported in IGD patients with PIGT mutations.…”

Case report of a child bearing a novel deleterious splicing variant in PIGT

“…Phenotypic features have included difficulty feeding, hypotonia, skeletal anomalies, renal cysts, seizures, esotropia, severe developmental delay, and dysmorphic features. [1,5–10] The PIGT gene encodes a subunit of the GPI transamidase, which catalyzes the transfer of fully assembled GPI units to proteins in the endoplasmic reticulum. [11]…”

First report of the neuropathological findings in a patient with leukodystrophy and compound heterozygous variants in the PIGT gene

“…GPI synthesis and GPI‐anchored protein modification are mediated by at least 29 genes and loss‐of‐function pathogenic variants in 19 of these genes have been described to cause neurological impairments including intellectual disability (ID), developmental delay (DD), epileptic seizures and multiple congenital anomalies . So far, 26 patients with a GPI anchor deficiency due to recessive PIGT variants have been described . The predominant clinical presentation is that of an epileptic encephalopathy including common but subtle craniofacial dysmorphisms and hypotrichosis, profound ID/DD, hypotonia, cortical visual impairment, nystagmus and cortical/cerebellar atrophy .…”