title: Molecular and clinical description of the first US patients with congenital disorder of glycosylation Ig.
abstract: In this report we describe the first two US patients with congenital disorder of glycosylation type Ig (CDG-Ig). Both patients presented with symptoms indicating CDG, including developmental delay, hypotonia and failure to thrive, and tested positive for deficient glycosylation of transferrin. Labeling of the patients' lipid-linked oligosaccharides suggested mutations in the hALG12 gene, encoding a mannosyltransferase. Both patients were shown to carry previously unpublished hALG12-mutations. Patient 1 has one allele with a deletion of G29, resulting in a premature stop codon, and another allele with an 824G>A mutation yielding an S275N amino acid change. Patient 2 carries two heterozygous mutations (688T>G and 931C>T), resulting in two amino acid exchanges, Y230D and R311C. An adenoviral vector expressing wild type hALG12 corrects the abnormal lipid-linked oligosaccharide pattern of the patients' cells. In addition to common CDG symptoms, these patients also presented with low IgG and genital hypoplasia, symptoms previously described in CDG-Ig patients. We therefore conclude that a combination of developmental delay, low IgG, and genital hypoplasia should prompt CDG testing.
authors.affiliation: The Burnham Institute, Glycobiology and Carbohydrate Chemistry Program, La Jolla, CA 92037, USA.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Eklund
authors.forename: John W
authors.initials: JW
authors.lastname: Newell
authors.forename: Liangwu
authors.initials: L
authors.lastname: Sun
authors.forename: Neung-Seon
authors.initials: NS
authors.lastname: Seo
authors.forename: Gulay
authors.initials: G
authors.lastname: Alper
authors.forename: Jessica
authors.initials: J
authors.lastname: Willert
authors.forename: Hudson H
authors.initials: HH
authors.lastname: Freeze
mesh_terms: D000015:Abnormalities, Multiple / Q000473:pathology*; D000256:Adenoviridae; D002478:Cells, Cultured; D018981:Congenital Disorders of Glycosylation / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers; D005816:Genetic Complementation Test; D005822:Genetic Vectors / Q000235:genetics; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007231:Infant, Newborn; D008297:Male; D008364:Mannosyltransferases / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009844:Oligosaccharides / Q000378:metabolism; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014481:United States
chemical_list: D017931:DNA Primers; D007074:Immunoglobulin G; D009844:Oligosaccharides; D008364:Mannosyltransferases