A novel donor splice site mutation in the glycogen debranching enzyme gene is associated with glycogen storage disease type III.
Analysis of glycogen debranching enzyme (debrancher) cDNA from a patient with glycogen storage disease type III revealed a deletion of 124 base pairs. A donor splice site mutation (IVS G+1 to T) was identified in the patient's debrancher gene, which caused exon skipping of the upstream exon and resulted in a truncated enzyme due to premature termination. Mutational analysis of the patient's family showed that this point mutation was inherited from the father. Southern blot analysis of the patient's genomic DNA showed an additional, unique EcoRI fragment of 5.8 kb, which was inherited from the mother. These results suggested that the patient was a compound heterozygote for the donor splice site mutation, which is the first identified in the debrancher gene, and had a genetic defect relating to an aberrant 5.8-kb EcoRI fragment.
Okubo
M
M
Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan.
Aoyama
Y
Y
Murase
T
T
D000328:Adult; D017398:Alternative Splicing; D001483:Base Sequence; D017931:DNA Primers; D015252:Deoxyribonucleases, Type II Site-Specific; D005091:Exons; D005260:Female; D006580:Genetic Carrier Screening; D006004:Glycogen Debranching Enzyme System / Q000235:genetics*; D006010:Glycogen Storage Disease Type III / Q000235:genetics*; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017384:Sequence Deletion
D017931:DNA Primers; D006004:Glycogen Debranching Enzyme System; C052155:endodeoxyribonuclease MnlI; D015252:Deoxyribonucleases, Type II Site-Specific