SEARCH:   Advanced

Blood, 1 April 2005, Vol. 105, No. 7, pp. 2671-2676. Prepublished online as a Blood First Edition Paper on December 2, 2004; DOI 10.1182/blood-2004-09-3509. This Article Full Text (PDF) All Versions of this Article: 2004-09-3509v1 105/7/2671    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Martinez-Duncker, I. Articles by Mollicone, R. Search for Related Content PubMed PubMed Citation Articles by Martinez-Duncker, I. Articles by Mollicone, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 9, 2004 Accepted November 26, 2004 Genetic complementation reveals a novel human congenital disorder of glycosylation of type II, due to inactivation of the Golgi CMP-sialic acid transporter Ivan Martinez-Duncker*, Thierry Dupre, Veronique Piller, Friedrich Piller, Jean-Jacques Candelier, Catherine Trichet, Gil Tchernia, Rafael Oriol, and Rosella Mollicone INSERM U504, GDR CNRS 2590, University of Paris Sud XI, Villejuif, France Laboratoire de biochimie A, Hopital Bichat, Claude Bernard AP-HP, Paris, France Laboratoire de biochimie A, Centre de Biophysique Moleculaire-CNRS UPR4301, Orleans, France Laboratoire d'Hematologie, Immunologie et Cytogenetique, Hopital Kremlin-Bicetre, Kremlin-Bicetre, France * Corresponding author; email: martinez{at}vjf.inserm.fr. We have identified a homozygous G >A substitution in the donor splice site of the intron 6 (IVS6+1G >A) of the CMP-sialic acid transporter gene of Lec2 cells, as the mutation responsible for their asialo-phenotype. These cells were used in complementation studies, to test the activity of the two CMP-sialic acid transporter cDNA alleles of a patient devoid of sialyl-Lex expression on polymorphonuclear cells. No complementation was obtained with either of the two patient alleles, whereas full restoration of the sialylated phenotype was obtained in the Lec2 cells transfected with the corresponding human wild type transcript. The inactivation of one patient allele, by a double microdeletion inducing a premature stop codon at position 327, and a splice mutation of the other allele inducing a 130 bp deletion and a premature stop codon at position 684, are proposed to be the causal defects of this disease. A four base insertion in the intron 6 was found in the mother and is proposed to be responsible for the splice mutation. We conclude that this defect is a new type of congenital disorder of glycosylation (CDG) of type IIf, affecting the transport of CMP-sialic acid into the Golgi. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Crispin, V. T. Chang, D. J. Harvey, R. A. Dwek, E. J. Evans, D. I. Stuart, E. Y. Jones, J. M. Lord, R. A. Spooner, and S. J. Davis A Human Embryonic Kidney 293T Cell Line Mutated at the Golgi {alpha}-Mannosidase II Locus J. Biol. Chem., August 7, 2009; 284(32): 21684 - 21695. [Abstract] [Full Text] [PDF] E. Jamroz, D. Adamek, J. Paprocka, M. Adamowicz, E. Marszal, and R. A. Wevers CDG Type Ia and Congenital Cytomegalovirus Infection: Two Coexisting Conditions J Child Neurol, January 1, 2009; 24(1): 13 - 18. [Abstract] [PDF] T. Miyazaki, K. Angata, P. H. Seeberger, O. Hindsgaul, and M. Fukuda CMP substitutions preferentially inhibit polysialic acid synthesis Glycobiology, February 1, 2008; 18(2): 187 - 194. [Abstract] [Full Text] [PDF] C. Perez-Cerda, D. Quelhas, A. I. Vega, J. Ecay, L. Vilarinho, and M. Ugarte Screening Using Serum Percentage of Carbohydrate-Deficient Transferrin for Congenital Disorders of Glycosylation in Children with Suspected Metabolic Disease Clin. Chem., January 1, 2008; 54(1): 93 - 100. [Abstract] [Full Text] [PDF] S. Wopereis, S. Grunewald, K. M.L.C. Huijben, E. Morava, R. Mollicone, B. G.M. van Engelen, D. J. Lefeber, and R. A. Wevers Transferrin and Apolipoprotein C-III Isofocusing Are Complementary in the Diagnosis of N- and O-Glycan Biosynthesis Defects Clin. Chem., February 1, 2007; 53(2): 180 - 187. [Abstract] [Full Text] [PDF] W. Zhao, T.-L. L. Chen, B. M. Vertel, and K. J. Colley The CMP-sialic Acid Transporter Is Localized in the Medial-Trans Golgi and Possesses Two Specific Endoplasmic Reticulum Export Motifs in Its Carboxyl-terminal Cytoplasmic Tail J. Biol. Chem., October 13, 2006; 281(41): 31106 - 31118. [Abstract] [Full Text] [PDF] D. Johnson and E. S. Bennett Isoform-specific Effects of the beta2 Subunit on Voltage-gated Sodium Channel Gating J. Biol. Chem., September 8, 2006; 281(36): 25875 - 25881. [Abstract] [Full Text] [PDF] C. Thiel, T. Lubke, G. Matthijs, K. von Figura, and C. Korner Targeted Disruption of the Mouse Phosphomannomutase 2 Gene Causes Early Embryonic Lethality Mol. Cell. Biol., August 1, 2006; 26(15): 5615 - 5620. [Abstract] [Full Text] [PDF] R. D. Cohn, E. Eklund, A. L. Bergner, J. F. Casella, S. L. Woods, J. Althaus, K. J. Blakemore, H. E. Fox, J. E. Hoover-Fong, A. Hamosh, et al. Intracranial Hemorrhage as the Initial Manifestation of a Congenital Disorder of Glycosylation Pediatrics, August 1, 2006; 118(2): e514 - e521. [Abstract] [Full Text] [PDF] Y. Helmus, J. Denecke, S. Yakubenia, P. Robinson, K. Luhn, D. L. Watson, P. J. McGrogan, D. Vestweber, T. Marquardt, and M. K. Wild Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose transporter Blood, May 15, 2006; 107(10): 3959 - 3966. [Abstract] [Full Text] [PDF] S. Wopereis, D. J. Lefeber, E. Morava, and R. A. Wevers Mechanisms in Protein O-Glycan Biosynthesis and Clinical and Molecular Aspects of Protein O-Glycan Biosynthesis Defects: A Review Clin. Chem., April 1, 2006; 52(4): 574 - 600. [Abstract] [Full Text] [PDF] B. Thomsen, P. Horn, F. Panitz, E. Bendixen, A. H. Petersen, L.-E. Holm, V. H. Nielsen, J. S. Agerholm, J. Arnbjerg, and C. Bendixen A missense mutation in the bovine SLC35A3 gene, encoding a UDP-N-acetylglucosamine transporter, causes complex vertebral malformation Genome Res., January 1, 2006; 16(1): 97 - 105. [Abstract] [Full Text] [PDF] S. Wopereis, E. Morava, S. Grunewald, M. Adamowicz, K. M. L. C. Huijben, D. J. Lefeber, and R. A. Wevers Patients with unsolved congenital disorders of glycosylation type II can be subdivided in six distinct biochemical groups Glycobiology, December 1, 2005; 15(12): 1312 - 1319. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020