title: Clinical and molecular characterization of the first adult congenital disorder of glycosylation (CDG) type Ic patient.
abstract: Congenital disorder of glycosylation (CDG) type Ic, the second largest subtype of CDG, is caused by mutations in human ALG6 (hALG6). This gene encodes the alpha1,3-glucosyltransferase that catalyzes transfer of the first glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. In this report, we describe the first adult patient diagnosed with CDG-Ic, carrying two previously unknown mutations. The first is a three base deletion (897-899delAAT) leading to the loss of I299, the second is an intronic mutation (IVS7 + 2T > G) that causes aberrant splicing. Wildtype hALG6, delivered by a lentiviral vector into patient's fibroblasts, clearly improves the biochemical phenotype, which confirms that the mutations are disease-causing. Striking clinical findings include limb deficiencies in the fingers, resembling brachydactyly type B, a deep vein thrombosis, pseudotumor cerebri, and endocrine disturbances with pronounced hyperandrogenism and virilization. However, even in adulthood, this patient shows normal magnetic resonance imaging of the brain.
authors: The Burnham Institute, La Jolla, CA 92037, USA.
authors: Liangwu
authors: L
authors: Sun
authors: Erik A
authors: EA
authors: Eklund
authors: Johan L K
authors: JL
authors: Van Hove
authors: Hudson H
authors: HH
authors: Freeze
authors: Janet A
authors: JA
authors: Thomas
mesh_terms: D000328:Adult; D001483:Base Sequence; D018981:Congenital Disorders of Glycosylation / Q000235:genetics / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005822:Genetic Vectors / Q000235:genetics; D005964:Glucosyltransferases / Q000235:genetics* / Q000378:metabolism; D006031:Glycosylation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D014162:Transfection
chemical_list: D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C498467:ALG6 protein, human; D005964:Glucosyltransferases; C119841:dolichyl pyrophosphate Man(9)GlcNAc(2) alpha1,3-glucosyltransferase