Primary adhalinopathy: a common cause of autosomal recessive muscular dystrophy of variable severity

Piccolo, F.; Roberds, Steven L.; Jeanpierre, Marc; Leturcq, F.; Azibi, K.; Beldjord, Chérif; Carrié, Alain; Récan, Dominique; Chaouch, Malika; Reghis, A.; Kerch, F. El; Sefïani, A.; Voït, Thomas; Merlini, Luciano; Collin, H Barry; Eymard, B.; Beckmann, Jacques S.; Romero, Norma B.; Tomé, Fernando; Fardeau, Michel; Campbell, Kevin P.; Jc, Kaplan

doi:10.1038/ng0695-243

Cited by 174 publications

(100 citation statements)

References 15 publications

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“…17 In non-consanguineous populations, ␣-sarcoglycan deficiency is the most frequent cause of autosomal recessive LGMD with a sarcoglycan defect (sarcoglycanopathy). [18][19][20] Thus, the development of therapeutic approaches in animal models for these diseases is a crucial step toward providing therapies for human patients. Because of their small size, virus-mediated delivery of the sarcoglycan genes can easily be achieved using either recombinant adenoviruses (Ad) or adenovirus-associated served.…”

Section: Introductionmentioning

confidence: 99%

Early adenovirus-mediated gene transfer effectively prevents muscular dystrophy in alpha-sarcoglycan-deficient mice

et al. 2000

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Limb-girdle muscular dystrophy type 2D (LGMD 2D) is the most common cause of LGMD with a sarcoglycan defect. We recently engineered a murine model for this progressive disease and we investigated the possibility of preventing the development of muscular dystrophy in these animals by adenovirus-mediated gene transfer of human ␣-sarcoglycan.Here we report that a single intramuscular injection of a first generation adenovirus into the skeletal muscle of neonate mice led to sustained expression of ␣-sarcoglycan at the sarcolemma of transduced myofibers for at least 7 months. The morphology of transduced muscles was consequently pre-

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Section: Introductionmentioning

confidence: 99%

Early adenovirus-mediated gene transfer effectively prevents muscular dystrophy in alpha-sarcoglycan-deficient mice

et al. 2000

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“…Sections were treated with avidin/biotin blocking solutions (Vector), blocked with 5% BSA in PBS for 30 min, and then incubated for 90 min with primary antibodies described above. After extensive washing with PBS, sections were incubated with biotinylated secondary antibodies for 30 ing with PBS, sections were mounted with FITC-guard (Testog) and observed under a Zeiss Axioplan fluorescence microscope. Photographs were taken under identical conditions with the same exposure time.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, mutations in at least two independent genes may cause SCARMD. The e~-sarcoglycan gene has been localized to chromosome 17q21 and mutations in this gene have been demonstrated to be responsible for SCARMD [28][29][30], also referred to limb-girdle muscular dystrophy type 2D (LGMD2D) [31]. Therefore, SCARMD linked to chromosome 13q12 has been suggested as caused by a defect in the 35 DAG gene although this protein has never been shown to be completely absent in SCARMD patients.…”

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confidence: 99%

“…Immunofluorescence analysis of skeletal muscle from LGMD2E patients showed a great reduction or absence of 13-sarcogtycan concomitant with a reduction of ~x-and 7-sarcoglycan. SCARMD linked to chromosome 13q12 has been renamed LGMD2C [30] and recently Noguchi et al [17] reported the identification of the 35 DAG gene on chromosome 13q12. Furthermore, they identified mutations in the y-sarcoglycan gene in LGMD2C.…”

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confidence: 99%

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Absence of γ‐sarcoglycan (35 DAG) in autosomal recessive muscular dystrophy linked to chromosome 13q12

et al. 1996

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We have partially sequenced rabbit skeletal muscle T-sarcoglycan an integral component of the dystrophin-glycoprotein complex. Specific antibodies were produced against a 7-sarcoglycan peptide and used to examine the expression of T-sarcoglycan in skeletal muscle of patients with severe childhood autosomal muscular dystrophy linked to chromosome 13q12 (SCARMD). We show by immunofluorescence and Western blotting that in skeletal muscle from these patients T-sarcoglycan is completely absent and c~-and ~-sarcoglycan are greatly reduced in abundance, whereas other components of the DGC are preserved. In addition, we show that in normal muscle ~-, ~-, and T-sarcoglycan constitute a tightly associated sarcolemma complex which can not be disrupted by SDS treatment.

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“…les are associated with a milder phenotype than homozygous null mutations (19,20,52). If the expression of the SGC is perturbed not only in the skeletal and cardiac fibers, but also in the smooth muscle of the vasculature of these patients, vascular dysfunction might play a role in the pathogenesis of LGMD.…”

Section: Discussionmentioning

confidence: 99%

Expression of γ-Sarcoglycan in Smooth Muscle and Its Interaction with the Smooth Muscle Sarcoglycan-Sarcospan Complex

Barresi¹,

Moore²,

Stolle³

et al. 2000

Journal of Biological Chemistry

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The sarcoglycan complex in striated muscle is a heterotetrameric unit integrally associated with sarcospan in the dystrophin-glycoprotein complex. The sarcoglycans, ␣, ␤, ␥, and ␦, are mutually dependent with regard to their localization at the sarcolemma, and mutations in any of the sarcoglycan genes lead to limb-girdle muscular dystrophies type 2C-2F. In smooth muscle ␤-and ␦-sarcoglycans are associated with ⑀-sarcoglycan, a glycoprotein homologous to ␣-sarcoglycan. Here, we demonstrate that ␥-sarcoglycan is also a component of the sarcoglycan complex in the smooth muscle. First, we show the presence of ␥-sarcoglycan in a number of smooth muscle-containing organs, and we verify the existence of identical transcripts in skeletal and smooth muscle. The specificity of the expression of ␥-sarcoglycan in smooth muscle was confirmed by analysis of smooth muscle cells in culture. Next, we provide evidence for the association of ␥-sarcoglycan with the sarcoglycan-sarcospan complex by biochemical analysis and comparison among animal models for muscular dystrophy. Moreover, we find disruption of the sarcoglycan complex in the vascular smooth muscle of a patient with ␥-sarcoglycanopathy. Taken together, our results prove that the sarcoglycan complex in vascular and visceral smooth muscle consists of ⑀-, ␤-, ␥-, and ␦-sarcoglycans and is associated with sarcospan.The sarcoglycan-sarcospan complex (SGC) 1 is part of the dystrophin-glycoprotein complex (DGC), a group of proteins well characterized in skeletal and cardiac muscle. The DGC also includes dystrophin, dystroglycan (␣-and ␤-), and syntrophins (for reviews see Refs. 1-4). Recently, other proteins such as dystrobrevin (5-7) and neuronal nitric-oxide synthase (8 -10) have been shown to correlate with the DGC at the sarcolemma. The interaction of the DGC with components of the extracellular matrix (11-13) may have an important role in force transmission and in sarcolemmal protection (14 -16). The importance of the SGC in maintaining the sarcolemmal stability is evident from the various forms of limb-girdle muscular dystrophy (LGMD) caused by mutations in any of the genes coding for the SGs (17-21). In addition, a functional role for the SGC in signaling has been hypothesized (22,23).Several mouse models of muscular dystrophy have been engineered in which ␣-(Sgca-null) (24, 25), ␤-(Sgcb-null) (26, 27), ␥-(Sgcg-null) (28), or ␦-SG (Sgcd-null) (29, 30) genes have been disrupted. In addition to the skeletal muscle pathology, all but the Sgca-null mice show a cardiomyopathic phenotype. Furthermore, a spontaneous mutant, the ␦-SG-deficient BIO14.6 hamster, has been studied as an animal model for dilated and hypertrophic cardiomyopathy (31, 32). Correspondingly, patients with defects in ␤-, ␥-, and ␦-SGs, but not ␣-SG, are occasionally affected by dilated cardiomyopathy (33)(34)(35).In skeletal and cardiac muscle, the SGC is a heterotetrameric unit composed of the transmembrane glycoproteins ␣-, ␤-, ␥-, and ␦-SGs. The synthesis of all four of the proteins is required in or...

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Primary adhalinopathy: a common cause of autosomal recessive muscular dystrophy of variable severity

Cited by 174 publications

References 15 publications

Early adenovirus-mediated gene transfer effectively prevents muscular dystrophy in alpha-sarcoglycan-deficient mice

Early adenovirus-mediated gene transfer effectively prevents muscular dystrophy in alpha-sarcoglycan-deficient mice

Absence of γ‐sarcoglycan (35 DAG) in autosomal recessive muscular dystrophy linked to chromosome 13q12

Expression of γ-Sarcoglycan in Smooth Muscle and Its Interaction with the Smooth Muscle Sarcoglycan-Sarcospan Complex

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