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Collagen Type VI Myopathies

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Progress in Heritable Soft Connective Tissue Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 802))

Abstract

Mutations in each of the three collagen VI genes COL6A1, COL6A2 and COL6A3 cause two main types of muscle disorders: Ullrich congenital muscular dystrophy, a severe phenotype, and a mild to moderate phenotype Bethlem myopathy. Recently, two additional phenotypes, including a limb-girdle muscular dystrophy phenotype and an autosomal recessive myosclerosis reported in one family with mutations in COL6A2 have been reported. Collagen VI is an important component of the extracellular matrix which forms a microfibrillar network that is found in close association with the cell and surrounding basement membrane. Collagen VI is also found in the interstitial space of many tissues including muscle, tendon, skin, cartilage, and intervertebral discs. Thus, collagen VI mutations result in disorders with combined muscle and connective tissue involvement, including weakness, joint laxity and contractures, and abnormal skin findings.

In this review we highlight the four recognized clinical phenotypes of collagen VI related – myopathies; Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM), autosomal dominant limb-girdle muscular dystrophy phenotype and autosomal recessive myosclerosis. We discuss the diagnostic criteria of these disorders, the molecular pathogenesis, genetics, treatment, and related disorders.

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Abbreviations

AD:

Autosomal Dominant

BM:

Bethlem Myopathy

CCD:

Central Core

CGH:

Comparative Genomic Hybridization

CMD:

Congenital Muscular Dystrophy

CsA:

Cyclosporine A

DGC:

Dystrophin-Glycoprotein Complex

ECM:

Extracellular Matrix

EDMD:

Emery-Dreifuss Muscular Dystrophy

EDS:

Ehlers-Danlos Syndrome

EMG:

Electromyography

GAPDH:

Glyceraldehyde 3-phosphate Dehydrogenase

LGMD:

Limb Girdle Muscular Dystrophy

MDC1A:

Merosin-Deficient Congenital Muscular Dystrophy Type 1A

MDC1C:

Congenital Muscular Dystrophy Type 1C

MDC1D:

Congenital Muscular Dystrophy Type 1D

MRI:

Magnetic Resonance Imaging

mRNA:

Messenger Ribonucleic Acid

PTP:

Permeability Transition Pore

siRNA:

Short Interfering Ribonucleic Acid

SR:

Sarcoplasmic Reticulum

TGF-β:

Transforming Growth Factor beta

UCMD:

Ullrich Congenital Muscular Dystrophy

vWFA:

von Willebrand Factor Type A

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Authors and Affiliations

  1. Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK

    Kate M. D. Bushby & Debbie Hicks

  2. Department of Pediatric Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, USA

    James Collins

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  1. Kate M. D. Bushby
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Correspondence to Kate M. D. Bushby .

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Editors and Affiliations

  1. Department of Pathology, The University of Georgia, Athens, Georgia, USA

    Jaroslava Halper

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Bushby, K.M.D., Collins, J., Hicks, D. (2014). Collagen Type VI Myopathies. In: Halper, J. (eds) Progress in Heritable Soft Connective Tissue Diseases. Advances in Experimental Medicine and Biology, vol 802. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7893-1_12

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