Mutations in MAGT1 lead to a glycosylation disorder with a variable phenotype

• DOI: 10.1073/pnas.1817815116
• Publication Date: 2019-04-30T03:53:27Z
• Authors: Eline Blommaert; Romain Péanne; Natalia A. Cherep...; Daisy Rymen; Frederik Staels; Jaak Jaeken; Valérie Race; Liesbeth Keldermans; Erika Souche; Anniek Corveleyn; Rebecca Sparkes; Kaustuv Bhattacharya; Christine Devalck; Rik Schrijvers; François Foulquier; Reid Gilmore; Gert Matthijs
• Keywords: Male; 0301 basic medicine; Adolescent; [SDV]Life Sciences [q-bio]; Tumor Suppressor Proteins; congenital disorders of glycosylation;CDG;XMEN;oligosaccharyltransferase complex; DNA Mutational Analysis; Membrane Proteins; Généralités; 3. Good health; 03 medical and health sciences; Congenital Disorders of Glycosylation; Hexosyltransferases; Humans; [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology; CDG; Congenital disorders of glycosylation; [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]; XMEN; Child; Oligosaccharyltransferase complex; Cation Transport Proteins

Congenital disorders of glycosylation (CDG) are a group rare metabolic diseases, due to impaired protein and lipid glycosylation. We identified two patients with defective serum transferrin mutations in the MAGT1 gene. These present phenotype that is mainly characterized by intellectual developmental disability. has been described be subunit oligosaccharyltransferase (OST) complex more specifically STT3B complex. However, it was also claimed magnesium (Mg2+) transporter. So far, were linked primary immunodeficiency, chronic EBV infections attributed Mg2+ homeostasis defect (XMEN). compared clinical cellular our an XMEN patient we recently identified. All three have N-glycosylation defect, as shown study different substrates, such GLUT1 SHBG, demonstrating posttranslational carried out dysfunctional all patients. Moreover, deficiency associated enhanced expression TUSC3, homolog MAGT1, pointing toward compensatory mechanism. Hence, delineate MAGT1-CDG disorder phenotypes caused defects