Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Molecular and clinical description of the first US patients with congenital disorder of glycosylation Ig

Eklund, Erik A LU ; Newell, John W ; Sun, Liangwu ; Seo, Neung-Seon ; Alper, Gulay ; Willert, Jessica and Freeze, Hudson H (2005) In Molecular Genetics and Metabolism 84(1). p.25-31
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 Both patients were shown to carry previously unpublished hALG12-mutations.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),... (More)

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 Both patients were shown to carry previously unpublished hALG12-mutations.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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Abnormalities, Multiple/pathology, Adenoviridae, Cells, Cultured, Congenital Disorders of Glycosylation/genetics, DNA Primers, Genetic Complementation Test, Genetic Vectors/genetics, Glycosylation, Humans, Immunoglobulin G/metabolism, Infant, Newborn, Male, Mannosyltransferases/genetics, Mutation, Missense/genetics, Oligosaccharides/metabolism, Protein Structure, Tertiary, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, United States
in
Molecular Genetics and Metabolism
volume
84
issue
1
pages
25 - 31
publisher
Elsevier
external identifiers
  • pmid:15639192
  • scopus:11444252182
ISSN
1096-7192
DOI
10.1016/j.ymgme.2004.09.014
language
English
LU publication?
no
id
625392cc-511d-4e48-a61e-0d909a56b2ee
date added to LUP
2021-10-12 00:07:33
date last changed
2024-06-01 18:25:36
@article{625392cc-511d-4e48-a61e-0d909a56b2ee,
  abstract     = {{<p>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&gt;A mutation yielding an S275N amino acid change. Patient 2 carries two heterozygous mutations (688T&gt;G and 931C&gt;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.</p>}},
  author       = {{Eklund, Erik A and Newell, John W and Sun, Liangwu and Seo, Neung-Seon and Alper, Gulay and Willert, Jessica and Freeze, Hudson H}},
  issn         = {{1096-7192}},
  keywords     = {{Abnormalities, Multiple/pathology; Adenoviridae; Cells, Cultured; Congenital Disorders of Glycosylation/genetics; DNA Primers; Genetic Complementation Test; Genetic Vectors/genetics; Glycosylation; Humans; Immunoglobulin G/metabolism; Infant, Newborn; Male; Mannosyltransferases/genetics; Mutation, Missense/genetics; Oligosaccharides/metabolism; Protein Structure, Tertiary; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; United States}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{25--31}},
  publisher    = {{Elsevier}},
  series       = {{Molecular Genetics and Metabolism}},
  title        = {{Molecular and clinical description of the first US patients with congenital disorder of glycosylation Ig}},
  url          = {{http://dx.doi.org/10.1016/j.ymgme.2004.09.014}},
  doi          = {{10.1016/j.ymgme.2004.09.014}},
  volume       = {{84}},
  year         = {{2005}},
}