Detailed mapping of the phosphomannomutase 2 (PMM2) gene and mutation detection enable improved analysis for Scandinavian CDG type I families

The gene for carbohydrate-deficient glycoprotein syndrome type I (CDG1) has previously been localised by us close to marker D16S406 in chromosome regi on 16p13.2-3. We also presented data indicating a strong founder mutation a ssociated with a specific haplotype in CDG I patients from western Scandina via. The phosphomannomutase 2 (PMM2) gene was recently put forward as a lik ely CDG1 candidate gene. We have now shown that the specific haplotype is a ssociated with the PMM2 mutation 357C>A. Using data from radiation hybrid p anel we have refined the position of the PMM2 gene to very close to marker D16S3020 in the interval between D16S406 and AFM282ze1 on the distal side a nd D16S3087 on the proximal side. Due to the severity of the disease many f amilies request prenatal diagnostic services for CDG I. In the meantime, un til the mutation spectrum is fully examined, we propose the combined use of mutation analysis and linkage analysis with polymorphic markers as diagnos tic tools for Scandinavian CDG I families requesting prenatal diagnosis. Us ing this strategy we have to date successfully performed 15 prenatal diagno ses for CDG I.