Effect of mutations found in carbohydrate-deficient glycoprotein syndrome type IA on the activity of phosphomannomutase 2

Seven mutant forms of human phosphomannomutase 2 were produced in Esclerich ia coli and purified. These mutants had a V-max of 0.2-50% of the wild enzy me and were unstable. The least active protein (R141H) bears a very frequen t mutation, which has never been found in the homozygous state whereas the second least active protein (D188G) corresponds to a mutation associated wi th a particularly severe phenotype, We conclude that total lack of phosphom annomutase 2 is incompatible with life. Another conclusion is that the elev ated residual phosphomannomutase activity found in fibroblasts of some pati ents is contributed by their mutated phosphomannomutase 2, (C) 1999 Federat ion of European Biochemical Societies.