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

✍ Scribed by Jianjun Shen; Yong Bao; Yuan-Tsong Chen

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 153 KB
• Volume: 9
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/(sici)1098-1004(1997)9:1<37::aid-humu6>3.0.co;2-m

✦ Synopsis

Glycogen storage disease type III (GSD-III) is an autosomal recessive disease resulting from deficient glycogen debranching enzyme (ODE) 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. Hum Mutat 9:37-40, 1997.