Myopathy and phosphorylase kinase deficiency caused by a mutation in thePHKA1 gene

Wuyts, Wim; Reyniers, Edwin; Ceuterick, C.; Storm, Katrien; Barsy, Thierry de; Martin, Jean‐Jacques

doi:10.1002/ajmg.a.30517

Cited by 31 publications

(19 citation statements)

References 9 publications

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“…9 The other three changes include a nonsense mutation (E1112X) truncating the PHKA1 protein by 111 amino acids, 7 a splice junction mutation causing skipping of one exon, 6 and a single nucleotide deletion at position 695 (695delC). 8 Studies of those patients had included forearm ischemic exercise test, electromyography, muscle biopsy, biochemical analysis of muscle extracts, and molecular genetic analysis, but this is the first investigation of muscle metabolism during dynamic exercise in a patient with a mutation in the ␣ M gene.…”

Section: Resultsmentioning

confidence: 99%

Is muscle glycogenolysis impaired in X-linked phosphorylase b kinase deficiency?

Ørngreen

Schelhaas²,

Jeppesen³

et al. 2008

Neurology

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Section: Resultsmentioning

confidence: 99%

Is muscle glycogenolysis impaired in X-linked phosphorylase b kinase deficiency?

Ørngreen

Schelhaas²,

Jeppesen³

et al. 2008

Neurology

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“…Allelic variants of Pla2g7 can promote reductions in adiposity following exercise in human populations [36], and reduction of adipose tissue is a known function of myocyte AR [37]. Allelic variants in Phka1 in human populations are associated with metabolic myopathy [38], [39]. When considered in the context of the putative protective or toxic functions of these genes, the general pattern of regulation observed in our samples for Ddit4l , Enah and Itgb1bp3 are consistent with adaptive tissue response to toxicity and that observed for Phka1 and Pla2g7 is consistent with a causal role in myopathy.…”

Section: Resultsmentioning

confidence: 99%

Microarray Analysis of Gene Expression by Skeletal Muscle of Three Mouse Models of Kennedy Disease/Spinal Bulbar Muscular Atrophy

Razak

Rao

et al. 2010

PLoS ONE

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BackgroundEmerging evidence implicates altered gene expression within skeletal muscle in the pathogenesis of Kennedy disease/spinal bulbar muscular atrophy (KD/SBMA). We therefore broadly characterized gene expression in skeletal muscle of three independently generated mouse models of this disease. The mouse models included a polyglutamine expanded (polyQ) AR knock-in model (AR113Q), a polyQ AR transgenic model (AR97Q), and a transgenic mouse that overexpresses wild type AR solely in skeletal muscle (HSA-AR). HSA-AR mice were included because they substantially reproduce the KD/SBMA phenotype despite the absence of polyQ AR.Methodology/Principal FindingsWe performed microarray analysis of lower hindlimb muscles taken from these three models relative to wild type controls using high density oligonucleotide arrays. All microarray comparisons were made with at least 3 animals in each condition, and only those genes having at least 2-fold difference and whose coefficient of variance was less than 100% were considered to be differentially expressed. When considered globally, there was a similar overlap in gene changes between the 3 models: 19% between HSA-AR and AR97Q, 21% between AR97Q and AR113Q, and 17% between HSA-AR and AR113Q, with 8% shared by all models. Several patterns of gene expression relevant to the disease process were observed. Notably, patterns of gene expression typical of loss of AR function were observed in all three models, as were alterations in genes involved in cell adhesion, energy balance, muscle atrophy and myogenesis. We additionally measured changes similar to those observed in skeletal muscle of a mouse model of Huntington's Disease, and to those common to muscle atrophy from diverse causes.Conclusions/SignificanceBy comparing patterns of gene expression in three independent models of KD/SBMA, we have been able to identify candidate genes that might mediate the core myogenic features of KD/SBMA.

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“…There are several reports of patients with muscle phosphorylase b kinase deficiency due to mutations in the PHKA1 gene, 115, 116, 118, 119, 121, 122 . Two features, however, suggest that the protein dysfunction causing muscle phosphorylase b kinase deficiency extends beyond mutations in PHKA1 and other genes encoding subunits of muscle phosphorylase b kinase protein.…”

Section: Genetic Causes Of Rhabdomyolysismentioning

confidence: 99%

Diagnostic evaluation of rhabdomyolysis

2015

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Rhabdomyolysis is characterized by severe acute muscle injury resulting in muscle pain, weakness, and/or swelling with release of myofiber contents into the bloodstream. Symptoms develop over hours to days following an inciting factor and may be associated with dark pigmentation of the urine. Serum creatine kinase and urine myoglobin levels are markedly elevated. The clinical examination, history, laboratory studies, muscle biopsy, and genetic testing are useful tools for diagnosis of rhabdomyolysis, and they can help differentiate acquired from inherited causes of rhabdomyolysis. Acquired causes include substance abuse, medication or toxic exposures, electrolyte abnormalities, endocrine disturbance, and autoimmune myopathies. Inherited predisposition to rhabdomyolysis can occur with disorders of glycogen metabolism, fatty acid beta-oxidation, and mitochondrial oxidative phosphorylation. Less common inherited causes of rhabdomyolysis include structural myopathies, channelopathies, and sickle cell disease. This review focuses on the differentiation of acquired and inherited causes of rhabdomyolysis and proposes a practical diagnostic algorithm.

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Myopathy and phosphorylase kinase deficiency caused by a mutation in thePHKA1 gene

Cited by 31 publications

References 9 publications

Is muscle glycogenolysis impaired in X-linked phosphorylase b kinase deficiency?

Is muscle glycogenolysis impaired in X-linked phosphorylase b kinase deficiency?

Microarray Analysis of Gene Expression by Skeletal Muscle of Three Mouse Models of Kennedy Disease/Spinal Bulbar Muscular Atrophy

Diagnostic evaluation of rhabdomyolysis

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