Molecular and clinical description of the first US patients with congenital disorder of glycosylation Ig
(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 Both patients were shown to carry previously unpublished hALG12-mutations.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 Both patients were shown to carry previously unpublished hALG12-mutations.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.
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- author
- Eklund, Erik A LU ; Newell, John W ; Sun, Liangwu ; Seo, Neung-Seon ; Alper, Gulay ; Willert, Jessica and Freeze, Hudson H
- publishing date
- 2005
- 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>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.</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}}, }