Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Mutations in the liver glycogen synthase gene in children with hypoglycemia due to glycogen storage disease type 0.

Authors: Orho, M  Bosshard, NU  Buist, NR  Gitzelmann, R  Aynsley-Green, A  Blumel, P  Gannon, MC  Nuttall, FQ  Groop, LC 
Citation: Orho M, etal., J Clin Invest. 1998 Aug 1;102(3):507-15.
Pubmed: (View Article at PubMed) PMID:9691087
DOI: Full-text: DOI:10.1172/JCI2890

Glycogen storage disease type 0 (GSD-0) is a rare form of fasting hypoglycemia presenting in infancy or early childhood and accompanied by high blood ketones and low alanine and lactate concentrations. Although feeding relieves symptoms, it often results in postprandial hyperglycemia and hyperlactatemia. The glycogen synthase (GS) activity has been low or immeasurable in liver biopsies, whereas the liver glycogen content has been only moderately decreased. To investigate whether mutations in the liver GS gene (GYS2) on chromosome 12p12.2 were involved in GSD-0, we determined the exon-intron structure of the GYS2 gene and examined nine affected children from five families for linkage of GSD-0 to the GYS2 gene. Mutation screening of the 16 GYS2 exons was done by single-strand conformational polymorphism (SSCP) and direct sequencing. Liver GS deficiency was diagnosed from liver biopsies (GS activity and glycogen content). GS activity in the liver of the affected children was extremely low or nil, resulting in subnormal glycogen content. After suggestive linkage to the GYS2 gene had been established (LOD score = 2.9; P < 0.01), mutation screening revealed several different mutations in these families, including a premature stop codon in exon 5 (Arg246X), a 5'-donor splice site mutation in intron 6 (G+1T--> CT), and missense mutations Asn39Ser, Ala339Pro, His446Asp, Pro479Gln, Ser483Pro, and Met491Arg. Seven of the affected children carried mutations on both alleles. The mutations could not be found in 200 healthy persons. Expression of the mutated enzymes in COS7 cells indicated severely impaired GS activity. In conclusion, the results demonstrate that GSD-0 is caused by different mutations in the GYS2 gene.

Annotation

Disease Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 1600764
Created: 2007-03-26
Species: All species
Last Modified: 2007-03-26
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.