RESEARCH ARTICLE


An Immunological Analysis of Dystroglycan Subunits: Lessons Learned from a Small Cohort of Non-Congenital Dystrophic Patients



Ernesto Pavoni#, 1, Francesca Sciandra1, Giorgio Tasca2, Roberta Tittarelli1, Manuela Bozzi3, Bruno Giardina1, 3, Enzo Ricci*, 2, 4, Andrea Brancaccio*, 1
1 CNR - Istituto di Chimica del Riconoscimento Molecolare c/o Istituto di Biochimica e Biochimica Clinica, Catholic University, Rome, Italy
2 Dipartimento di Neuroscienze, Catholic University, Rome Italy
3 Istituto di Biochimica e Biochimica Clinica, Catholic University, Rome, Italy
4 Fondazione Don Gnocchi, Rome, Italy


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© Pavoni et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to these authors at the CNR - Istituto di Chimica del Riconoscimento Molecolare c/o Istituto di Biochimica e Biochimica Clinica, Catholic University, L.go F. Vito 1, 00168 Rome, Italy; Tel: +39-06-3057612; Fax: +39-06-3053598; E-mail: andrea.brancaccio@icrm.cnr.it Dipartimento di Neuroscienze, Catholic University, L.go A. Gemelli 8, 00168 Rome, Italy; Tel: +39-06-30154303; Fax: +39-06-35501909; E-mail: ericci@rm.unicatt.it
# Present Address: Unità NeuroGlia, DIBIT, HSR, Via Olgettina 58, 20132 Milan, Italy.


Abstract

The dystroglycan (DG) expression pattern can be altered in severe muscular dystrophies. In fact, some congenital muscular dystrophies (CMDs) and limb-girdle muscular dystrophies (LGMDs) are caused by point mutations identified in six glycosyltransferase genes which are likely to target different steps along the posttranslational “O-glycosylation route” leading to a fully decorated and functional α-DG subunit. Indeed, hypoglycosylation of α-DG is thought to represent a major pathological event, in that it could reduce the DG’s ability to bind the basement membrane components, thus leading to sarcolemmal instability and necrosis. In order to set up an efficient standard immunological protocol, taking advantage of a wide panel of antibodies, we have analyzed the two DG subunits in a small cohort of adult dystrophic patients, whom an extensive medical examination had already clinically classified as affected by LGMD (5), Miyoshi (1) or distal (1) myopathy. Immunofluorescence analysis of skeletal muscle tissue sections revealed a proper sarcolemmal localization of the DG subunits in all the patients analyzed. However, Western blot analysis of lectin enriched skeletal muscle samples revealed an abnormal glycosylation of α-DG in two patients. Our work reinforces the notion that a careful immunological and biochemical analysis of the two DG subunits should be always considered as a prerequisite for the identification of new putative cases of dystroglycanopathy.

Keywords: Dystroglycan, limb-girdle muscular dystrophy, distal myopathy, Miyoshi myopathy, secondary dystroglycanopathies, dystrophin-glycoprotein complex.