Disease relevance of GBE1

• Genetic mapping of GBE1 and its association with glycogen storage disease IV in American Quarter horses [1].
• A novel missense mutation in the glycogen branching enzyme gene in a child with myopathy and hepatopathy [2].
• Glycogen storage disease type IV or Andersen disease is an autosomal recessive disorder due to deficiency of glycogen branching enzyme [3].
• Mutational heterozygosity in the glycogen brancher enzyme gene has not been previously reported as a cause for this rare disease [4].
• Glycogen branching enzyme in Lafora myoclonus epilepsy [5].

High impact information on GBE1

• Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen-branching enzyme gene [6].
• Three point mutations in the GBE gene were found in two patients with the classical presentation: R515C, F257L, and R524X [6].
• Novel missense mutations in the glycogen-branching enzyme gene in adult polyglucosan body disease [7].
• We describe the first non-Ashkenazi patient with adult polyglucosan body disease and decreased glycogen-branching enzyme (GBE) activity in leukocytes [7].
• Possible candidate genes in this region include GBE1 and ACOX2, which encode enzymes involved in glycogen and fatty acid metabolism, respectively [8].

Chemical compound and disease context of GBE1

• BACKGROUND: Glycogen storage disease type IV (GSD-IV) is a clinically heterogeneous autosomal recessive disorder due to glycogen branching enzyme (GBE) deficiency and resulting in the accumulation of an amylopectin-like polysaccharide [9].

Biological context of GBE1

• A polymorphic microsatellite (GBEms1) in a GBE1 BAC clone was then identified and genetically mapped to ECA26 on the Animal Health Trust full-sibling equine reference family [1].
• This data provides strong molecular genetic support for the candidacy of the GBE1 locus in equine GSD IV [1].
• The infant had a homozygous single nucleotide deletion in the open reading frame of GBE1 gene [10].
• Brancher enzyme activity may be normal or only mildly reduced in leukocytes in Ashkenazi patients with PBD, implying genetic heterogeneity [11].
• Biochemical and genetic analyses demonstrated reduced glycogen brancher enzyme levels associated with a heterozygous point mutation (Tyr329Ser or Y329S) in the glycogen brancher enzyme gene on chromosome 3 [4].

Anatomical context of GBE1

• Studies of the residual glycogen branching enzyme activity present in human skin fibroblasts from patients with type IV glycogen storage disease [12].
• Prenatal diagnosis has occasionally been performed by the measurement of the GBE activity in cultured chorionic villi (CV) cells [13].
• We describe a patient with ultrastructural characteristics consistent with glycogenosis type IV, but with normal brancher enzyme activity in dermal fibroblasts and cardiac muscle [14].
• This further implies that when polyglucosan inclusions are observed within myofibers it is mandatory to examine the muscle tissue for brancher enzyme activity since the brancher enzyme activities in circulating erythrocytes and leucocytes were normal in all three affected siblings and their parents [15].
• Normal skeletal muscle and liver tissue histology and GBE activity, normal GBE activity in skin fibroblasts, plus normal GBE gene sequence in this patient exclude the classical branching enzyme deficiency (type IV GSD) [16].

Associations of GBE1 with chemical compounds

• The patient was heterozygous for a G-to-A substitution at codon 524 (R524Q), changing an encoded arginine (CGA) to glutamine (CAA), while the GBE1 gene on the other allele was not expressed [2].
• We have now derived the complete GBE1 cDNA sequences for control horses and affected foals, and identified a C to A substitution at base 102 that results in a tyrosine (Y) to stop (X) mutation in codon 34 of exon 1 [17].
• The identification, among expressed genes, of putative sequences for glycogen synthase, glycogen branching enzyme, chitin synthase, and for the first enzyme in chitin synthesis (glutamine fructose-6-phosphate aminotransferase) is reported [18].
• The transgenic starches were specifically modified with respect to amylopectin chain length and phosphorous content by suppression of the starch branching enzyme and overexpression of glycogen branching enzyme [19].

Analytical, diagnostic and therapeutic context of GBE1

• We report two novel truncating mutations, as well as the first genomic mutational analysis of GBE1 using denaturing high performance liquid chromatography [20].
• Using the mouse Affymetrix gene chip, we found that 1,4-alpha-glucan branching enzyme 1 (GBE1) was one of the most up-regulated genes following nickel exposure [21].
• The fatal neonatal form of type IV glycogen storage disease (GSD IV) was diagnosed on light and electron microscopy and by analysis of GBE1 , the gene encoding glycogen branching enzyme [20].

References