Glycogenin-2 Is Dispensable for Liver Glycogen Synthesis and Glucagon-Stimulated Glucose Release

Irgens, Henrik; Fjeld, Karianne; Johansson, Bente B.; Ringdal, Monika; Immervoll, Heike; Leh, Sabine; Søvik, Oddmund; Johansson, Stefan; Molven, Anders; Njølstad, Pål R.

doi:10.1210/jc.2014-4337

Cited by 11 publications

(9 citation statements)

References 22 publications

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“…Another group studied the effect of a similar deletion on liver function (11 members of two families and one blood donor) and found no gross abnormalities. 9 Although their assay lacked the resolution to define the breakpoints of the deletion, their results were compatible with the esv2662319 deletion. XG is homologous to CD99 and therefore it is speculated they share similar cell adhesion and migration functions.…”

Section: Discussionmentioning

confidence: 91%

“…Mensah et al found no clinical abnormalities in the participants of their study; however, they did not investigate if these persons had intact XG or GYG2 . Another group studied the effect of a similar deletion on liver function (11 members of two families and one blood donor) and found no gross abnormalities . Although their assay lacked the resolution to define the breakpoints of the deletion, their results were compatible with the esv2662319 deletion.…”

Section: Discussionmentioning

confidence: 99%

“…Using this model, two sets of primers were designed to amplify across the deletion: a structural variant detection (SVD) reaction with a predicted 714‐bp amplicon size (SVD‐short) or a 3555‐bp amplicon size (SVD‐long). All primers were designed with computer software (Primer‐BLAST) with the exception of primers for GYG2 and KCNJ11 , which were previously reported . XG exons and coding sequences were designated based on the reference NCBI transcript NM_001141919.1.…”

Section: Methodsmentioning

confidence: 99%

“…All primers were designed with computer software (Primer-BLAST) 8 with the exception of primers for GYG2 and KCNJ11, which were previously reported. 9 XG exons and coding sequences were designated based on the reference NCBI transcript NM_001141919.1. Primers were synthesized by Eurofins Genomics or Thermo Fisher Scientific.…”

Section: Polymerase Chain Reactionmentioning

confidence: 99%

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A large deletion spanning XG and GYG2 constitutes a genetic basis of the Xg_null phenotype, underlying anti‐Xg^a production

et al. 2019

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BACKGROUND The PBDX/XG gene encoding the Xga blood group antigen was described in 1994, but the genetic determinant of XG expression on RBCs was reported only in 2018. However, the frequencies of Xg(a−) individuals could not explain the rarity of anti‐Xga makers. We therefore sought to elucidate the molecular basis of the Xg(a−) phenotype in people producing anti‐Xga. STUDY DESIGN AND METHODS Two genomic DNA (gDNA) and 13 plasma‐derived cell‐free DNA (cfDNA) samples from anti‐Xga makers were investigated (14 males and one female). PBDX/XG exon sequencing was attempted on one gDNA sample. Polymerase chain reaction assays were developed and bioinformatics used to define a suspected deletion in all samples. RESULTS Investigation of one gDNA sample revealed a 114‐kb deletion (esv2662319) on the X chromosome that spans XG exons 4 through 10 and the downstream GYG2 gene. A 3555‐bp fragment bridging this deletion was amplified to confirm its presence. Another deletion‐specific polymerase chain reaction of 714 bp enabled identification of esv2662319 in both gDNA samples and eight cfDNA samples while ruling it out in one cfDNA. Males were hemizygous for esv2662319 and the female likely homozygous. Four cfDNA sample results were inconclusive, probably due to poor sample quality. Sanger sequencing recognized the recombination junctions as a heterogeneous LTR6B sequence. CONCLUSION We identified a large deletion on the X chromosome, resulting in a true, tissue‐wide Xgnull phenotype. This deletion was found in 10 of 11 anti‐Xga makers from which DNA could be amplified. One sample remained unexplained, indicating further heterogeneity to be explored.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Polymerase Chain Reactionmentioning

confidence: 99%

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A large deletion spanning XG and GYG2 constitutes a genetic basis of the Xg_null phenotype, underlying anti‐Xg^a production

et al. 2019

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“…To date, no impact on liver function has been reported, and glycogen storage such as seen in the biopsy from patient 1 may be subclinical. This may be due to glycogenin-2 that is expressed in the liver, although the importance of glycogenin-2 has been debated (Irgens et al 2015). In previously described patients, at least 32 loss-of-function (nonsense and splice site) variants in the 38 GYG1 alleles were identified.…”

Section: Discussionmentioning

confidence: 99%

Cardiomyopathy as presenting sign of glycogenin‐1 deficiency—report of three cases and review of the literature

Hedberg‐Oldfors

Glamuzina

Ruygrok

et al. 2016

J of Inher Metab Disea

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We describe a new type of cardiomyopathy caused by a mutation in the glycogenin-1 gene (GYG1). Three unrelated male patients aged 34 to 52 years with cardiomyopathy and abnormal glycogen storage on endomyocardial biopsy were homozygous for the missense mutation p.Asp102His in GYG1. The mutated glycogenin-1 protein was expressed in cardiac tissue but had lost its ability to autoglucosylate as demonstrated by an in vitro assay and western blot analysis. It was therefore unable to form the primer for normal glycogen synthesis. Two of the patients showed similar patterns of heart dilatation, reduced ejection fraction and extensive late gadolinium enhancement on cardiac magnetic resonance imaging. These two patients were severely affected, necessitating cardiac transplantation. The cardiomyocyte storage material was characterized by large inclusions of periodic acid and Schiff positive material that was partly resistant to alpha-amylase treatment consistent with polyglucosan. The storage material had, unlike normal glycogen, a partly fibrillar structure by electron microscopy. None of the patients showed signs or symptoms of muscle weakness but a skeletal muscle biopsy in one case revealed muscle fibres with abnormal glycogen storage. Glycogenin-1 deficiency is known as a rare cause of skeletal muscle glycogen storage disease, usually without cardiomyopathy. We demonstrate that it may also be the cause of severe cardiomyopathy and cardiac failure without skeletal muscle weakness. GYG1 should be included in cardiomyopathy gene panels.Electronic supplementary materialThe online version of this article (doi:10.1007/s10545-016-9978-1) contains supplementary material, which is available to authorized users.

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Glycogen metabolism and structure: A review

Neoh,

Tan,

Chen

et al. 2024

Carbohydrate Polymers

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Glycogenin-2 Is Dispensable for Liver Glycogen Synthesis and Glucagon-Stimulated Glucose Release

Abstract: This is the first evaluation of humans without GN2 expression. Our data indicate that GN2 is not required for liver glycogen synthesis and glucagon-stimulated glucose release.

Cited by 11 publications

References 22 publications

A large deletion spanning XG and GYG2 constitutes a genetic basis of the Xg_null phenotype, underlying anti‐Xg^a production

A large deletion spanning XG and GYG2 constitutes a genetic basis of the Xg_null phenotype, underlying anti‐Xg^a production

Cardiomyopathy as presenting sign of glycogenin‐1 deficiency—report of three cases and review of the literature

Glycogen metabolism and structure: A review

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Glycogenin-2 Is Dispensable for Liver Glycogen Synthesis and Glucagon-Stimulated Glucose Release

Abstract: This is the first evaluation of humans without GN2 expression. Our data indicate that GN2 is not required for liver glycogen synthesis and glucagon-stimulated glucose release.

Cited by 11 publications

References 22 publications

A large deletion spanning XG and GYG2 constitutes a genetic basis of the Xgnull phenotype, underlying anti‐Xga production

A large deletion spanning XG and GYG2 constitutes a genetic basis of the Xgnull phenotype, underlying anti‐Xga production

Cardiomyopathy as presenting sign of glycogenin‐1 deficiency—report of three cases and review of the literature

Glycogen metabolism and structure: A review

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A large deletion spanning XG and GYG2 constitutes a genetic basis of the Xg_null phenotype, underlying anti‐Xg^a production

A large deletion spanning XG and GYG2 constitutes a genetic basis of the Xg_null phenotype, underlying anti‐Xg^a production