The Human Liver Glycogen Synthase Isozyme Gene Is Located on the Short Arm of Chromosome 12

Nuttall, Frank Q.; Gannon, Mary C.; Kubic, Virginia; Hoyt, Kari J.

doi:10.1006/geno.1994.1086

Cited by 20 publications

(19 citation statements)

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“…A number of other genes previously proposed as candidates we also considered less likely because they map outside the SROA (Table 1). Some of these candidates were plausible, like LGS, encoding the rate limiting enzyme in the synthesis of glycogen (Nuttall et al, 1994) and LDHB, encoding lactate dehydrogenase type B (Li et al, 1988). Glycogen is found abundantly in carcinoma in situ and the majority of the di erent invasive components (Mosto® et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Identification of the critical region of 12p over-representation in testicular germ cell tumors of adolescents and adults

et al. 1998

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Cytogenetically, testicular germ cell tumors of adolescents and adults (TGCTs) are characterized by gain of 12p-sequences, most often through isochromosome formation (i(12p)). Fluorescence in situ hybridization (FISH) has shown that i(12p))-negative TGCTs also cryptically contain extra 12p-sequences. The consistency of 12p-over-representation in all histological subtypes of TGCTs, including their preinvasive stage, suggests that gain of one or more genes on 12p is crucial in the development of this cancer. So far, studies aimed at the identi®cation of the relevant gene(s) were based on thè candidate-gene approach'. No convincing evidence in favor of or against a particular gene has been reported. We combined conventional karyotyping, comparative genomic hybridization, and FISH to identify TGCTs with ampli®cations of restricted regions of 12p. Out of 49 primary TGCTs (23 without i(12p), 13 with and 13 unknown), eight tumors (six without i(12p) and two unknown) showed ampli®cations corresponding to 12p11.1-p12.1. Using bicolour-FISH, physical mapping, and semi-quantitative polymerase chain reactions, the size of the shortest region of overlap of ampli®cation (SROA) was estimated to be between 1750 ± 3000 kb. In addition, we mapped a number of genes in and around this region. While fourteen known genes could be excluded as candidates based on their location outside this region, we demonstrate that KRAS2, JAW1 and SOX5 genes are localized within the SROA. While KRAS2 and JAW1 map to the proximal border of the SROA, SOX5 maps centrally in the SROA. KRAS2 and JAW1 are expressed in all TGCTs, whereas one 12p amplicon-positive TGCT lacks expression of SOX5. The critical region of 12p over-represented in TGCTs is less than 8% of the total length of the short arm of chromosome 12. It will be helpful in the identi®cation of the gene(s) involved in TGCT-development.

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Section: Discussionmentioning

confidence: 99%

Identification of the critical region of 12p over-representation in testicular germ cell tumors of adolescents and adults

et al. 1998

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“…After linkage to the chromosomal region 12p12.2 (9) had been established, we screened the coding regions, the exon-intron boundary regions, and part of the putative promoter of the GYS2 gene for mutations. Mutations were found in all affected children, indicating that GSD-0 is caused by molecular defects in the GYS2 gene.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 1998

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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 ϭ 2.9; P Ͻ 0.01), mutation screening revealed several different mutations in these families, including a premature stop codon in exon 5 (Arg246X), a 5 Ј -donor splice site mutation in intron 6 (G

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“…[3] When no other cases had been recognized for 14 years, the existence of GSD0 was doubted, and investigators suggested that deficiency of hepatic glycogen synthase is not compatible with life. [10,11] It has become apparent that GSD0 may not invariably be the devastating disorder that was initially described. Many of the problems originally attributed to GSD0 were probably caused by prematurity of the index cases and not by GSD0 per se.…”

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Hepatic glycogen synthase deficiency: An infrequently recognized cause of ketotic hypoglycemia

Weinstein

Correia

Saunders

et al. 2006

Molecular Genetics and Metabolism

110

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The glycogen storage diseases comprise several inherited diseases caused by abnormalities of enzymes that regulate the synthesis or degradation of glycogen. In contrast to the classic hepatic glycogen storage diseases that are characterized by fasting hypoglycemia and hepatomegaly, the liver is not enlarged in GSD0. Patients with GSD0 typically have fasting ketotic hypoglycemia without prominent muscle symptoms. Most children are cognitively and developmentally normal. Short stature and osteopenia are common features, but other long-term complications, common in other types of GSD, have not been reported in GSD0. Until recently, the definitive diagnosis of GSD0 depended on the demonstration of decreased hepatic glycogen on a liver biopsy. The need for an invasive procedure may be one reason that this condition has been infrequently diagnosed. Mutation analysis of the GYS2 gene (12p12.2) is a non-invasive method for making this diagnosis in patients suspected to have this disorder. This mini-review discusses the pathophysiology of this disorder, use of mutation analysis to diagnose GSD0, and the clinical characteristics of all reported cases of GSD0.

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The Human Liver Glycogen Synthase Isozyme Gene Is Located on the Short Arm of Chromosome 12

Cited by 20 publications

References 0 publications

Identification of the critical region of 12p over-representation in testicular germ cell tumors of adolescents and adults

Identification of the critical region of 12p over-representation in testicular germ cell tumors of adolescents and adults

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

Hepatic glycogen synthase deficiency: An infrequently recognized cause of ketotic hypoglycemia

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