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

摘要

>Seven mutant forms of human phosphomannomutase 2 were produced in Escherichia coli and purified. These mutants had a V _max 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.