{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:50:16Z","timestamp":1788367816845,"version":"build-2803163510"},"reference-count":42,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JND"],"published-print":{"date-parts":[[2020,9,18]]},"abstract":"<jats:p>Collagen VI-related dystrophies (COL6-RDs) and Duchenne muscular dystrophy (DMD) cause progressive muscle weakness and disability. COL6-RDs are caused by mutations in the COL6 genes (COL6A1, COL6A2 and COL6A3) encoding the extracellular matrix protein collagen VI, and DMD is caused by mutations in the DMD gene encoding the cytoplasmic protein dystrophin. Both COL6-RDs and DMD are characterized by infiltration of the muscles by fatty and fibrotic tissue. This study examined the effect of disease pathology on skeletal muscles in lower extremity muscles of COL6-RDs using timed functional tests, strength measures and qualitative\/ quantitative magnetic resonance imaging\/spectroscopy measures (MRI\/MRS) in comparison to unaffected (control) individuals. Patients with COL6-RD were also compared to age and gender matched patients with DMD. Patients with COL6-RD presented with a typical pattern of fatty infiltration of the muscle giving rise to an apparent halo effect around the muscle, while patients with DMD had evidence of fatty infiltration throughout the muscle areas imaged. Quantitatively, fat fraction, and transverse relaxation time (T2) were elevated in both COL6-RD and DMD patients compared to unaffected (control) individuals. Patients with COL6-RD had widespread muscle atrophy, likely contributing to weakness. In contrast, patients with DMD revealed force deficits even in muscle groups with increased contractile areas.<\/jats:p>","DOI":"10.3233\/jnd-190457","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T13:38:41Z","timestamp":1591709921000},"page":"407-417","source":"Crossref","is-referenced-by-count":12,"title":["Lower Extremity Muscle Involvement in the Intermediate and Bethlem Myopathy Forms of COL6-Related Dystrophy and Duchenne Muscular Dystrophy: A Cross-Sectional Study"],"prefix":"10.1177","volume":"7","author":[{"given":"Abhinandan","family":"Batra","sequence":"first","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donovan J.","family":"Lott","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Willcocks","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean C.","family":"Forbes","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Triplett","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jahannaz","family":"Dastgir","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pomi","family":"Yun","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Reghan Foley","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten G.","family":"B\u00f6nnemann","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"Vandenborne","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn A.","family":"Walter","sequence":"additional","affiliation":[{"name":"Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"issue":"7","key":"10.3233\/JND-190457_ref1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrneurol.2011.81","article-title":"The collagen VI-related myopathies: Muscle meets its matrix","volume":"7","author":"B\u00f6nnemann","year":"2011","journal-title":"Nature Reviews Neurology"},{"issue":"9","key":"10.3233\/JND-190457_ref2","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1136\/jmg.2002.002311","article-title":"Collagen VI related muscle disorders","volume":"42","author":"Lampe","year":"2005","journal-title":"J Med Genet"},{"issue":"2","key":"10.3233\/JND-190457_ref3","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.crad.2006.08.012","article-title":"MRI for the demonstration of subclinical muscle involvement in muscular dystrophy","volume":"62","author":"Sookhoo","year":"2007","journal-title":"Clinical Radiology"},{"issue":"1","key":"10.3233\/JND-190457_ref4","doi-asserted-by":"crossref","first-page":"51","DOI":"10.5858\/arpa.2014-0453-OA","article-title":"Common Data Elements for Muscle Biopsy Reporting","volume":"140","author":"Dastgir","year":"2015","journal-title":"Archives of Pathology & Laboratory Medicine"},{"issue":"3","key":"10.3233\/JND-190457_ref5","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/mus.23902","article-title":"THE 6-minute walk test and other endpoints in Duchenne muscular dystrophy: Longitudinal natural history observations over 48 weeks from a multicenter study","volume":"48","author":"McDonald","year":"2013","journal-title":"Muscle & Nerve"},{"issue":"7","key":"10.3233\/JND-190457_ref6","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.nmd.2009.06.368","article-title":"Reliability of the North Star Ambulatory Assessment in a multicentric setting","volume":"19","author":"Mazzone","year":"2009","journal-title":"Neuromuscular Disorders"},{"issue":"10","key":"10.3233\/JND-190457_ref7","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1111\/j.1469-8749.2012.04345.x","article-title":"A critical review of functional assessment tools for upper limbs in Duchenne muscular dystrophy","volume":"54","author":"Mazzone","year":"2012","journal-title":"Developmental Medicine & Child Neurology"},{"issue":"3","key":"10.3233\/JND-190457_ref8","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.nmd.2013.11.014","article-title":"Reliability of the Performance of Upper Limb assessment in Duchenne muscular dystrophy","volume":"24","author":"Pane","year":"2014","journal-title":"Neuromuscul Disord"},{"issue":"7","key":"10.3233\/JND-190457_ref9","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.apmr.2010.03.024","article-title":"Age-Related Differences in Lower-Limb Muscle Cross-Sectional Area and Torque Production in Boys With Duchenne Muscular Dystrophy","volume":"91","author":"Mathur","year":"2010","journal-title":"Archives of Physical Medicine and Rehabilitation"},{"issue":"1","key":"10.3233\/JND-190457_ref10","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/1471-2377-12-91","article-title":"Quantitative muscle strength assessment in duchenne muscular dystrophy: Longitudinal study and correlation with functional measures","volume":"12","author":"Lerario","year":"2012","journal-title":"BMC Neurology"},{"issue":"1","key":"10.3233\/JND-190457_ref11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.nmd.2014.09.010","article-title":"Results of a two-year pilot study of clinical outcome measures in collagen VI- and laminin alpha2-related congenital muscular dystrophies","volume":"25","author":"Meilleur","year":"2015","journal-title":"Neuromuscular Disorders"},{"issue":"2","key":"10.3233\/JND-190457_ref12","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/(SICI)1099-0496(200002)29:2<141::AID-PPUL9>3.0.CO;2-Y","article-title":"Pulmonary manifestations of neuromuscular disease with special reference to Duchenne muscular dystrophy and spinal muscular atrophy","volume":"29","author":"Gozal","year":"2000","journal-title":"Pediatr Pulmonol"},{"issue":"5","key":"10.3233\/JND-190457_ref13","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/ppul.23172","article-title":"Characterization of pulmonary function in Duchenne Muscular Dystrophy","volume":"50","author":"Mayer","year":"2015","journal-title":"Pediatr Pulmonol"},{"issue":"6","key":"10.3233\/JND-190457_ref14","doi-asserted-by":"crossref","first-page":"e0128915","DOI":"10.1371\/journal.pone.0128915","article-title":"Magnetic Resonance Assessment of Hypertrophic and Pseudo-Hypertrophic Changes in Lower Leg Muscles of Boys with Duchenne Muscular Dystrophy and Their Relationship to Functional Measurements","volume":"10","author":"Vohra","year":"2015","journal-title":"PLOS ONE"},{"issue":"15","key":"10.3233\/JND-190457_ref15","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.4103\/0366-6999.186638","article-title":"\u201cTarget\u201d and \u201cSandwich\u201d Signs in Thigh Muscles have High Diagnostic Values for Collagen VI-related Myopathies","volume":"129","author":"Fu","year":"2016","journal-title":"Chin Med J (Engl)"},{"issue":"4","key":"10.3233\/JND-190457_ref16","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.nmd.2005.01.004","article-title":"Muscle MRI in Ullrich congenital muscular dystrophy and Bethlem myopathy","volume":"15","author":"Mercuri","year":"2005","journal-title":"Neuromuscular Disorders"},{"issue":"2","key":"10.3233\/JND-190457_ref17","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/jmri.20804","article-title":"Muscle MRI in inherited neuromuscular disorders: Past, present, and future","volume":"25","author":"Mercuri","year":"2007","journal-title":"Journal of Magnetic Resonance Imaging"},{"issue":"4","key":"10.3233\/JND-190457_ref18","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1002\/ana.24599","article-title":"Multicenter prospective longitudinal study of magnetic resonance biomarkers in a large duchenne muscular dystrophy cohort","volume":"79","author":"Willcocks","year":"2016","journal-title":"Ann Neurol"},{"issue":"2","key":"10.3233\/JND-190457_ref19","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/ana.21846","article-title":"Muscle magnetic resonance imaging involvement in muscular dystrophies with rigidity of the spine","volume":"67","author":"Mercuri","year":"2010","journal-title":"Ann Neurol"},{"issue":"1","key":"10.3233\/JND-190457_ref20","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1148\/radiol.13121948","article-title":"Skeletal muscles of ambulant children with Duchenne muscular dystrophy: Validation of multicenter study of evaluation with MR imaging and MR spectroscopy","volume":"269","author":"Forbes","year":"2013","journal-title":"Radiology"},{"issue":"5","key":"10.3233\/JND-190457_ref21","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.nmd.2013.12.012","article-title":"Longitudinal measurements of MRI-T2 in boys with Duchenne muscular dystrophy: Effects of age and disease progression","volume":"24","author":"Willcocks","year":"2014","journal-title":"Neuromuscular Disorders"},{"issue":"3","key":"10.3233\/JND-190457_ref24","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s10278-004-1014-6","article-title":"OsiriX: An Open-Source Software for Navigating in Multidimensional DICOM Images","volume":"17","author":"Md","year":"2004","journal-title":"Journal of Digital Imaging"},{"issue":"6","key":"10.3233\/JND-190457_ref25","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1109\/TMI.2010.2046908","article-title":"N4ITK: Improved N3 bias correction","volume":"29","author":"Tustison","year":"2010","journal-title":"IEEE Trans Med Imaging"},{"issue":"1","key":"10.3233\/JND-190457_ref26","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.nmd.2011.06.750","article-title":"Relationships of thigh muscle contractile and non-contractile tissue with function, strength, and age in boys with Duchenne muscular dystrophy","volume":"22","author":"Akima","year":"2012","journal-title":"Neuromuscular Disorders"},{"issue":"7","key":"10.3233\/JND-190457_ref27","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.nmd.2014.03.013","article-title":"Assessment of intramuscular lipid and metabolites of the lower leg using magnetic resonance spectroscopy in boys with Duchenne muscular dystrophy","volume":"24","author":"Lott","year":"2014","journal-title":"Neuromuscular Disorders"},{"issue":"11","key":"10.3233\/JND-190457_ref28","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1212\/WNL.0000000000000775","article-title":"Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS","volume":"83","author":"Arpan","year":"2014","journal-title":"Neurology"},{"issue":"5 Suppl","key":"10.3233\/JND-190457_ref29","doi-asserted-by":"crossref","first-page":"S70","DOI":"10.1097\/00002060-199509001-00003","article-title":"Profiles of neuromuscular diseases. Duchenne muscular dystrophy","volume":"74","author":"McDonald","year":"1995","journal-title":"Am J Phys Med Rehabil"},{"issue":"4","key":"10.3233\/JND-190457_ref30","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/mus.21544","article-title":"The 6-minute walk test as a new outcome measure in Duchenne muscular dystrophy","volume":"41","author":"McDonald","year":"2010","journal-title":"Muscle & Nerve"},{"issue":"1","key":"10.3233\/JND-190457_ref31","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/mrm.24917","article-title":"Chemical shift-based MRI to measure fat fractions in dystrophic skeletal muscle","volume":"72","author":"Triplett","year":"2013","journal-title":"Magn Reson Med"},{"issue":"11","key":"10.3233\/JND-190457_ref32","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1038\/nm.2247","article-title":"Autophagy is defective in collagen VI muscular dystrophies, and its reactivation rescues myofiber degeneration","volume":"16","author":"Grumati","year":"2010","journal-title":"Nat Med"},{"issue":"12","key":"10.3233\/JND-190457_ref33","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.4161\/auto.7.12.17877","article-title":"Physical exercise stimulates autophagy in normal skeletal muscles but is detrimental for collagen VI-deficient muscles","volume":"7","author":"Grumati","year":"2011","journal-title":"Autophagy"},{"issue":"2","key":"10.3233\/JND-190457_ref34","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1006\/excr.1996.0328","article-title":"Collagen VI Regulates Normal and Transformed Mesenchymal Cell Proliferation in Vitro","volume":"228","author":"Atkinson","year":"1996","journal-title":"Experimental cell research"},{"issue":"10","key":"10.3233\/JND-190457_ref35","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1097\/NEN.0b013e31826c6f7b","article-title":"Muscle Fiber Atrophy and Regeneration Coexist in Collagen VI-Deficient Human Muscle: Role of Calpain-3 and Nuclear Factor-\u03baB Signaling","volume":"71","author":"Paco","year":"2012","journal-title":"Journal of Neuropathology & Experimental Neurology"},{"key":"10.3233\/JND-190457_ref36","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1038\/ncomms2964","article-title":"Collagen VI regulates satellite cell self-renewal and muscle regeneration","volume":"4","author":"Urciuolo","year":"2013","journal-title":"Nat Commun"},{"issue":"5","key":"10.3233\/JND-190457_ref37","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.nmd.2014.01.015","article-title":"Quantitative MRI and strength measurements in the assessment of muscle quality in Duchenne muscular dystrophy","volume":"24","author":"Wokke","year":"2014","journal-title":"Neuromuscul Disord"},{"issue":"2","key":"10.3233\/JND-190457_ref38","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/jgs.12653","article-title":"Difference in muscle quality over the adult life span and biological correlates in the Baltimore Longitudinal Study of Aging","volume":"62","author":"Moore","year":"2014","journal-title":"J Am Geriatr Soc"},{"issue":"7221","key":"10.3233\/JND-190457_ref40","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nature07414","article-title":"Sarcolemma-localized nNOS is required to maintain activity after mild exercise","volume":"456","author":"Kobayashi","year":"2008","journal-title":"Nature"},{"issue":"1","key":"10.3233\/JND-190457_ref41","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/path.4054","article-title":"Sildenafil reduces respiratory muscle weakness and fibrosis in the mdx mouse model of Duchenne muscular dystrophy","volume":"228","author":"Percival","year":"2012","journal-title":"J Pathol"},{"issue":"2","key":"10.3233\/JND-190457_ref42","doi-asserted-by":"crossref","first-page":"C230","DOI":"10.1152\/ajpcell.00199.2003","article-title":"Contractile function, sarcolemma integrity, and the loss of dystrophin after skeletal muscle eccentric contraction-induced injury","volume":"286","author":"Lovering","year":"2004","journal-title":"American Journal of Physiology - Cell Physiology"},{"issue":"5","key":"10.3233\/JND-190457_ref43","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1113\/jphysiol.2010.201921","article-title":"Lateral transmission of force is impaired in skeletal muscles of dystrophic mice and very old rats","volume":"589","author":"Ramaswamy","year":"2011","journal-title":"The Journal of Physiology"},{"issue":"20","key":"10.3233\/JND-190457_ref44","doi-asserted-by":"crossref","first-page":"14320","DOI":"10.1074\/jbc.M112.433078","article-title":"COL6A3 protein deficiency in mice leads to muscle and tendon defects similar to human collagen VI congenital muscular dystrophy","volume":"288","author":"Pan","year":"2013","journal-title":"J Biol Chem"},{"issue":"2","key":"10.3233\/JND-190457_ref45","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/nen.0b013e3181634ef7","article-title":"Muscle interstitial fibroblasts are the main source of collagen VI synthesis in skeletal muscle: Implications for congenital muscular dystrophy types Ullrich and Bethlem","volume":"67","author":"Zou","year":"2008","journal-title":"J Neuropathol Exp Neurol"}],"container-title":["Journal of Neuromuscular Diseases"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JND-190457","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:49:30Z","timestamp":1777506570000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JND-190457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,18]]},"references-count":42,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.3233\/jnd-190457","relation":{},"ISSN":["2214-3599","2214-3602"],"issn-type":[{"value":"2214-3599","type":"print"},{"value":"2214-3602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,18]]}}}