A nonsense mutation due to a single base insertion in the 3'-coding region of glycogen debranching enzyme gene associated with a severe phenotype in a patient with glycogen storage disease type IIIa.
Glycogen storage disease type III (GSD-III) is an autosomal recessive disease resulting from deficient glycogen debranching enzyme (GDE) activity. A child with GDE deficient in both liver and muscle (GSD-IIIa) had recurrent hypoglycemia, seizures, severe cardiomegaly, and hepatomegaly and died at 4 years of age. Analysis of the GDE gene in this child by single-strand conformation polymorphism, followed by direct DNA sequencing and restriction analysis, revealed an insertion of a nucleotide A into position 4529 of the GDE cDNA (4529insA). This insertion resulted in substitution of a tyrosine to a stop codon at amino acid 1510 (Y1510X). The 4529insA mutation appeared to be homozygous in this patient and was not found in 20 unrelated controls or 18 other GSD-III patients (14 GSD-IIIa and 4 GSD-IIIb). This is the first identification of a disease mutation in this gene, and the data suggest that homozygous 4529insA may be associated with a severe phenotype in GSD-IIIa.
Shen
J
J
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
Bao
Y
Y
Chen
Y T
YT
D006004:Glycogen Debranching Enzyme System / Q000235:genetics*; D006010:Glycogen Storage Disease Type III / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
D006004:Glycogen Debranching Enzyme System