GLYCOGEN-STORAGE-DISEASE TYPE-II - IDENTIFICATION OF A DINUCLEOTIDE DELETION AND A COMMON MISSENSE MUTATION IN THE LYSOSOMAL ALPHA-GLUCOSIDASE GENE

In nine Dutch patients with the infantile form of glycogen storage dis ease type IT (GSDII), who were compound heterozygous for either 525del T or exon18del (1), sequence analysis was performed to search for the mutations in the second lysosomal alpha-glucosidase allele. One patien t had a novel TG deletion at cDNA position 379 + 380. Surprisingly fiv e of the nine patients had the same two base pair changes: A921 --> T and G925 --> A. The first change is a well-known polymorphism but the second one is a novel mutation and results in the substitution of Gly3 09 by Arg. By screening 43 other GSDII patients the same mutation was found in two other cases, one from The Netherlands and one from France . To verify its deleterious effect, the mutation was introduced in the wild type lysosomal alpha-glucosidase cDNA and expressed in COS cells .