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Clinical and molecular characterization of the first adult congenital disorder of glycosylation (CDG) type Ic patient

Sun, Liangwu ; Eklund, Erik A LU ; Van Hove, Johan L K ; Freeze, Hudson H and Thomas, Janet A (2005) In American Journal of Medical Genetics. Part A 137A(1). p.22-26
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... (More)

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.

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author
; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Adult, Base Sequence, Congenital Disorders of Glycosylation/genetics, DNA Mutational Analysis, Female, Fibroblasts/metabolism, Genetic Vectors/genetics, Glucosyltransferases/genetics, Glycosylation, Green Fluorescent Proteins/genetics, Humans, Membrane Proteins/genetics, Mutation, Recombinant Fusion Proteins/genetics, Spectrometry, Mass, Electrospray Ionization, Transfection
in
American Journal of Medical Genetics. Part A
volume
137A
issue
1
pages
22 - 26
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:16007612
  • scopus:23344439462
ISSN
1552-4825
DOI
10.1002/ajmg.a.30831
language
English
LU publication?
no
id
76488e06-7fa6-4b48-8149-ddbd9e45cef8
date added to LUP
2021-10-12 00:06:16
date last changed
2024-01-05 18:00:44
@article{76488e06-7fa6-4b48-8149-ddbd9e45cef8,
  abstract     = {{<p>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 &gt; 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.</p>}},
  author       = {{Sun, Liangwu and Eklund, Erik A and Van Hove, Johan L K and Freeze, Hudson H and Thomas, Janet A}},
  issn         = {{1552-4825}},
  keywords     = {{Adult; Base Sequence; Congenital Disorders of Glycosylation/genetics; DNA Mutational Analysis; Female; Fibroblasts/metabolism; Genetic Vectors/genetics; Glucosyltransferases/genetics; Glycosylation; Green Fluorescent Proteins/genetics; Humans; Membrane Proteins/genetics; Mutation; Recombinant Fusion Proteins/genetics; Spectrometry, Mass, Electrospray Ionization; Transfection}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{22--26}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{American Journal of Medical Genetics. Part A}},
  title        = {{Clinical and molecular characterization of the first adult congenital disorder of glycosylation (CDG) type Ic patient}},
  url          = {{http://dx.doi.org/10.1002/ajmg.a.30831}},
  doi          = {{10.1002/ajmg.a.30831}},
  volume       = {{137A}},
  year         = {{2005}},
}