A NOVEL DONOR SPLICE-SITE MUTATION IN THE GLYCOGEN DEBRANCHING ENZYMEGENE IS ASSOCIATED WITH GLYCOGEN-STORAGE-DISEASE TYPE-III

Analysis of glycogen debranching enzyme (debrancher) cDNA from a patie nt with glycogen storage disease type III revealed a deletion of 124 b ase pairs. A donor splice site mutation (IVS G(+1) to T) was identifie d in the patient's debrancher gene, which caused exon skipping of the upstream exon and resulted in a truncated enzyme due to premature term ination. Mutational analysis of the patient's family showed that this point mutation was inherited from the father. Southern blot analysis o f the patient's genomic DNA showed an additional, unique EcoRI fragmen t of 5.8 kb, which was inherited from the mother. These results sugges ted that the patient was a compound heterozygote for the donor splice site mutation, which is the first identified in the debrancher gene, a nd had a genetic defect relating to an aberrant 5.8-kb EcoRI fragment. (C) 1996 Academic Press, Inc.