PRENATAL-DIAGNOSIS IN CDG1 FAMILIES - BEWARE OF HETEROGENEITY

Carbohydrate-deficient glycoprotein syndrome type I (CDG1) is an autos omal recessive, metabolic disorder with severe psychomotor retardation and a high mortality rate in early childhood. Most patients have a de ficiency of phosphomannomutase, due to mutations in PMM2, a gene locat ed on chromosome 16p13, Over a period of 18 months we offered prenatal diagnosis to eight families. In six cases and prior to the identifica tion of the gene, the diagnosis was based on linkage analysis and phos phomannomutase measurements. Subsequently direct mutation analysis has been used in two families. It is shown here that phosphomannomutase a ctivities are strongly reduced in cultured amniocytes and trophoblasts of affected foetuses, We refrained from offering prenatal testing in two other families, because either the disease did not link to chromos ome 16 and/or normal phosphomannomutase activities were measured in fi broblasts from the proband, This confirms earlier suggestions of heter ogeneity for CDG1.