FINE MAPPING OF THE GENE FOR CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROME, TYPE I (CDG1) - LINKAGE DISEQUILIBRIUM AND FOUNDER EFFECT IN SCANDINAVIAN FAMILIES

Carbohydrate-deficient glycoprotein syndrome type I (CDG I) is charact erized clinically by severe nervous system involvement and biochemical ly by defects in the carbohydrate residues in a number of serum glycop roteins. The CDG1 gene was recently localized by us to a 13-cM interva l in chromosome region 16p13. In this study 44 CDG I families from nin e countries were analyzed with available markers in a region ranging h om marker D16S495 to D16S497, and haplotype and linkage disequilibrium analyses were performed, One specific haplotype was found to be marke dly overrepresented in CDG I patients from a geographically distinct r egion in Scandinavia, strongly indicating that CDG I families in this region share the same ancestral CDG1 mutation. Furthermore, analysis o f the extent of the common haplotype in these families indicates that the CDG1 gene is located in the region defined by markers D16S513-AFMa 284wd5-D16S768-D16S406-D16S502., The critical CDG1 region, in strong l inkage disequilibrium with markers AFMa284wd5, D16S768, and D16S406, t hus constitutes less than 1 Rib of DNA and less than 1 cM in the very distal part of the CDG1 region defined by us previously. (C) 1997 Acad emic Press.