Seven mutant forms of human phosphomannomutase 2 were produced in Escherichia coli and purified. These mutants had a Vmax of 0.2-50% of the wild enzyme and were unstable. The least active protein (R141H) bears a very frequent mutation, which has never been found in the homozygous state whereas the second least active protein (D188G) corresponds to a mutation associated with a particularly severe phenotype. We conclude that total lack of phosphomannomutase 2 is incompatible with life. Another conclusion is that the elevated residual phosphomannomutase activity found in fibroblasts of some patients is contributed by their mutated phosphomannomutase 2.
Jaeken J, Matthijs G, Barone R, Carchon H, Carbohydrate deficient glycoprotein (CDG) syndrome type I., 10.1136/jmg.34.1.73
Van Schaftingen, FEBS Lett., 337, 318 (1995)
Jaeken J., Artigas J., Barone R., Fiumara A., de Koning T. J., Poll-The B. T., de Rijk-van Andel J. F., Hoffmann G. F., Assmann B., Mayatepek E., Pineda M., Vilaseca M. A., Saudubray J. M., Schlüter B., Wevers R., Van Schaftingen E., 10.1023/a:1005331523477
Powell L D, Paneerselvam K, Vij R, Diaz S, Manzi A, Buist N, Freeze H, Varki A, Carbohydrate-deficient glycoprotein syndrome: not an N-linked oligosaccharide processing defect, but an abnormality in lipid-linked oligosaccharide biosynthesis?, 10.1172/jci117540
Yamashita, J. Biol. Chem., 268, 5783 (1993)
Matthijs Gert, Schollen Els, Pardon Els, Veiga-Da-Cunha Maria, Jaeken Jaak, Cassiman Jean-Jacques, Schaftingen Emile Van, Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13 in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome), 10.1038/ng0597-88
Martinsson, Hum. Mol. Genet., 3, 2037 (1994)
Matthijs Gert, Legius Eric, Schollen Els, Vandenberk Petra, Jaeken Jaak, Barone Rita, Fiumara Agata, Visser Gepke, Lambert Marie, Cassiman Jean-Jacques, Evidence for Genetic Heterogeneity in the Carbohydrate-Deficient Glycoprotein Syndrome Type I (CDG1), 10.1006/geno.1996.0404
Matthijs Gert, Schollen Els, Van Schaftingen Emile, Cassiman Jean-Jacques, Jaeken Jaak, Lack of Homozygotes for the Most Frequent Disease Allele in Carbohydrate-Deficient Glycoprotein Syndrome Type 1A, 10.1086/301763
Pirard Michel, Collet Jean-François, Matthijs Gert, Van Schaftingen Emile, Comparison of PMM1 with the phosphomannomutases expressed in rat liver and in human cells, 10.1016/s0014-5793(97)00704-7
Veiga-da-Cunha Maria, Courtois Stephane, Michel Alain, Gosselain Eric, Van Schaftingen Emile, Amino Acid Conservation in Animal Glucokinases : IDENTIFICATION OF RESIDUES IMPLICATED IN THE INTERACTION WITH THE REGULATORY PROTEIN, 10.1074/jbc.271.11.6292
PIRARD Michel, ACHOURI Younes, COLLET Jean-François, SCHOLLEN Els, MATTHIJS Gert, SCHAFTINGEN Emile VAN, Kinetic properties and tissular distribution of mammalian phosphomannomutase isozymes, 10.1042/bj3390201
Sanger F., Nicklen S., Coulson A. R., DNA sequencing with chain-terminating inhibitors, 10.1073/pnas.74.12.5463
Studier F.William, Moffatt Barbara A., Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes, 10.1016/0022-2836(86)90385-2
Bradford Marion M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, 10.1016/0003-2697(76)90527-3
Collet Jean-François, Stroobant Vincent, Pirard Michel, Delpierre Ghislain, Van Schaftingen Emile, A New Class of Phosphotransferases Phosphorylated on an Aspartate Residue in an Amino-terminal DXDX(T/V) Motif, 10.1074/jbc.273.23.14107
Kjaergaard Susanne, Skovby Flemming, Schwartz Marianne, Absence of homozygosity for predominant mutations in PMM2 in Danish patients with carbohydrate-deficient glycoprotein syndrome type 1, 10.1038/sj.ejhg.5200194
Bjursell Cecilia, Wahlström Jan, Berg Kerstin, Stibler Helena, Kristiansson Bengt, Matthijs Gert, Martinsson Tommy, Detailed mapping of the phosphomannomutase 2 (PMM2) gene and mutation detection enable improved analysis for Scandinavian CDG type I families, 10.1038/sj.ejhg.5200234
Bibliographic reference
Pirard, Michèle ; Matthijs, Gert ; Heykants, Leen ; Schollen, Els ; Grünewald, Stephanie ; et. al. Effect of mutations found in carbohydrate-deficient glycoprotein syndrome type IA on the activity of phosphomannomutase 2.. In: FEBS letters, Vol. 452, no. 3, p. 319-22 (1999)