Congenital Megaconial Myopathy Due to a Novel Defect in the Choline Kinase beta (CHKB) Gene (P01.116)

Ríos, Purificación Gutiérrez; Kalra, Arun; Wilson, Jon D.; Tanji, Kurenai; Akman, Hasan O.; Area‐Gómez, Estela; Schon, Eric A.; DiMauro, Salvatore

doi:10.1212/wnl.78.1_meetingabstracts.p01.116

Cited by 7 publications

(6 citation statements)

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“…A recent study has established that the forelimb deformity in CHKB-deficient mice is due to altered growth plate physiology in the embryo, implicating a role for CHKB in endochondral bone formation (42). Homozygous and compound heterozygous mutations in CHKB have been identified in patients with congenital muscular dystrophy (17)(18)(19)43).…”

Section: Discussionmentioning

confidence: 99%

Choline Kinase β Mutant Mice Exhibit Reduced Phosphocholine, Elevated Osteoclast Activity, and Low Bone Mass

Kular¹,

Tickner²,

Pavlos

et al. 2015

Journal of Biological Chemistry

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Background: Bone homeostasis requires constant remodeling by bone-resorbing osteoclasts and bone-forming osteoblasts. Results: Choline kinase ␤ (CHKB)-deficient mice have reduced bone mass, increased osteoclast number, and impaired osteoblast function. Conclusion: CHKB activity controls bone homeostasis via regulation of osteoclasts and osteoblasts. Significance: This is the first report implicating a role for CHKB in bone homeostasis.

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Section: Discussionmentioning

confidence: 99%

Choline Kinase β Mutant Mice Exhibit Reduced Phosphocholine, Elevated Osteoclast Activity, and Low Bone Mass

Kular¹,

Tickner²,

Pavlos

et al. 2015

Journal of Biological Chemistry

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“…The enlarged mitochondria are potentially due to compensation for defective mitochondria in Chkb mutant cells [24]. The impaired phospholipid metabolism in the mitochondria-associated inner membrane was correlated with the abnormal size and aberrant cellular localisation of muscle mitochondria [25].…”

Section: The Role Of Chkβmentioning

confidence: 97%

Molecular structure and differential function of choline kinases CHKα and CHKβ in musculoskeletal system and cancer

Chen

Qiu

Wang

et al. 2017

Cytokine & Growth Factor Reviews

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Choline, a hydrophilic cation, has versatile physiological roles throughout the body, including cholinergic neurotransmission, memory consolidation and membrane biosynthesis and metabolism. Choline kinases possess enzyme activity that catalyses the conversion of choline to phosphocholine, which is further converted to cytidine diphosphate-coline (CDP-choline) in the biosynthesis of phosphatidylcholine (PC). PC is a major constituent of the phospholipid bilayer which constitutes the eukaryotic cell membrane, and regulates cell signal transduction. Choline Kinase consists of three isoforms, CHKα1, CHKα2 and CHKβ, encoded by two separate genes (CHKA(Human)/Chka(Mouse) and CHKB(Human)/Chkb(Mouse)). Both isoforms have similar structures and enzyme activity, but display some distinct molecular structural domains and differential tissue expression patterns. Whilst Choline Kinase was discovered in early 1950, its pivotal role in the development of muscular dystrophy, bone deformities, and cancer has only recently been identified. CHKα has been proposed as a cancer biomarker and its inhibition as an anti-cancer therapy. In contrast, restoration of CHKβ deficiency through CDP-choline supplements like citicoline may be beneficial for the treatment of muscular dystrophy, bone metabolic diseases, and cognitive conditions. The molecular structure and expression pattern of Choline Kinase, the differential roles of Choline Kinase isoforms and their potential as novel therapeutic targets for muscular dystrophy, bone deformities, cognitive conditions and cancer are discussed.

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“…The relationship between phospholipid and mitochondrial abnormalities could be mediated via the MAM, as several proteins involved in mitochondrial dynamics are an integral part of MAM, and MAM dysfunction may mediate increase in size and intracellular displacement of mitochondria 25,116,117 . In most cases mild dystrophic changes are consistently present in biopsies.…”

Section: Myopathology In Novel Mitochondrial Diseasesmentioning

confidence: 99%

Pathology of Adult and Paediatric Mitochondrial Myopathies

Phadke¹

2017

Preprint

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Mitochondria are dynamic organelles ubiquitously present in nucleated eukaryotic cells, subserving multiple metabolic functions, including cellular ATP generation by oxidative phosphorylation (OXPHOS). The OXPHOS machinery comprises five transmembrane respiratory chain enzyme complexes (RC). Defective OXPHOS gives rise to mitochondrial diseases (mtD). The incredible phenotypic and genetic diversity of mtD can be attributed at least in part to the RC dual genetic control (nuclear DNA [nDNA] and mitochondrial DNA [mtDNA]) and the complex interaction between the two genomes. Despite the increasing use of next-generation-sequencing (NGS) and various -omics platforms in unraveling novel mtD genes and pathomechanisms, current clinical practice for investigating mtD essentially involves a multipronged approach including clinical assessment, metabolic screening, imaging, pathological, biochemical and functional testing to guide molecular genetic analysis. This review addresses the broad muscle pathology landscape including genotype-phenotype correlations in adult and paediatric mtD, the role of immunodiagnostics in understanding some of the pathomechanisms underpinning the canonical features of mtD, and recent diagnostic advances in the field.

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Congenital Megaconial Myopathy Due to a Novel Defect in the Choline Kinase beta (CHKB) Gene (P01.116)

Cited by 7 publications

References 0 publications

Choline Kinase β Mutant Mice Exhibit Reduced Phosphocholine, Elevated Osteoclast Activity, and Low Bone Mass

Choline Kinase β Mutant Mice Exhibit Reduced Phosphocholine, Elevated Osteoclast Activity, and Low Bone Mass

Molecular structure and differential function of choline kinases CHKα and CHKβ in musculoskeletal system and cancer

Pathology of Adult and Paediatric Mitochondrial Myopathies

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