β–sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex

Bönnemann, Carsten G.; Modi, Raju; Noguchi, S.; Mizuno, Yuji; Yoshida, Motoaki; Gussoni, Emanuela; McNally, Elizabeth M.; Duggan, David; Angelini, C.; Hoffman, Eric P.; Ozawa, Eijiro; Kunkel, Louis M.

doi:10.1038/ng1195-266

Cited by 406 publications

(254 citation statements)

References 44 publications

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“…1 For example, dystrophin, a 427 kDa protein which links the F-actin to transmembrane components of the DGC, is mutated in the X-linked Duchenne muscular dystrophy (DMD) and in the milder Becker muscular dystrophy (BMD), while the transmembrane glycoproteins, a-, b-, g-and dsarcoglycans, are mutated in several recessive forms of limb-girdle muscular dystrophies (LGMD2D, E, C and F, respectively). [2][3][4][5][6][7][8] These disorders are characterized clinically by an increase in serum creatine kinase level and an involvement of specific groups of muscles, especially those of proximal part of the limbs, that is often associated with pseudo-hypertrophy of the calves. The dystrophic features in muscle biopsies present as fibers with central nucleation reflecting regeneration, inflammatory infiltrates, fiber splitting, fibrosis and necrosis.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive monitoring of therapeutic gene transfer in animal models of muscular dystrophies

et al. 2005

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Muscular dystrophies are a genetically and phenotypically heterogeneous group of degenerative muscle diseases. A subset of them are due to genetic deficiencies in proteins which form the dystrophin-associated complex at the membrane of the myofibers. In this report, we utilized recombinant adeno-associated virus containing a U7 cassette carrying an antisense sequence aimed at inducing exon skipping of the dystrophin gene or containing the a-sarcoglycan gene to alleviate the dystrophic phenotype of the mdx and Sgca-null mice, respectively. As these diseases are characterized by cycle of degeneration/regeneration, we postulated that a reporter gene coadministered at the time of the treatment would make it possible to follow the extent of muscle repair. We observed that the murine secreted alkaline phosphatase (muSeAP) level was very much lower in these animal models than in normal mice. Upon treatment of the dystrophic muscle by gene transfer, the level of muSeAP was restored and correlated with the expression of the therapeutic transgene and with the level of muscle improvement. The system described here provides a simple and noninvasive procedure for monitoring the outcome of a therapeutic strategy involving cell survival.

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Section: Introductionmentioning

confidence: 99%

Noninvasive monitoring of therapeutic gene transfer in animal models of muscular dystrophies

et al. 2005

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“…[1][2][3][4][5][6][7][8] Mutations in four genes encoding sarcoglycan proteins (␣-, ␤-, ␥-and ␦-SG) are responsible for various forms of autosomal recessive limb-girdle muscular dystrophy (LGMD 2D, 2E, 2C and 2F, respectively). [9][10][11][12][13][14][15][16] This heterogeneous group of diseases nevertheless shares a common feature in that a primary deficiency of any of the sarcoglycan proteins leads to the reduction or the absence of all other members of the SG-SSPN complex. 17 In non-consanguineous populations, ␣-sarcoglycan deficiency is the most frequent cause of autosomal recessive LGMD with a sarcoglycan defect (sarcoglycanopathy).…”

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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“…Sarcoglycan, a major component of the DAG complex, 3,4 is composed of at least four transmembrane glycoproteins: α-sarcoglycan (formerly called 50 kDa DAG or adhalin), 5,6 , -sarcoglycan (43 DAG), 7,8 γ-sarcoglycan (35 DAG) 9 and δ-sarcoglycan (35 kDa). 10 The muscular dystrophies that arise from mutations in α-, -, γ-and δ-sarcoglycan genes are classified as the LGMD type 2D, E, C and F, respectively.…”

Section: Introductionmentioning

confidence: 99%

Severe limb girdle muscular dystrophy in Spanish gypsies: further evidence for a founder mutation in the γ-sarcoglycan gene

et al. 1998

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Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscular dystrophy with primary γ-sarcoglycan deficiency, generally associated with a severe clinical course. γ-sarcoglycan, a 35 kDa dystrophinassociated protein, is encoded by a single gene on chromosome 13q12. Six different mutations have been described in that gene, and it has been proved they are the origin of the disease. One of these mutations (C283Y), a G ® A transition in codon 283, was recently and exclusively identified in Gypsy patients from different European countries. We report the study of 11 LGMD2C unrelated Gypsy families (nine Spanish and two Portugese). The muscle biopsies of these patients showed a drastically decreased immunostaining with α and γ-sarcoglycan antibodies. All the patients were homozygous for C283Y missense mutation, and all affected chromosomes (patients and heterozygous relatives) carried the allele 5 (112 bp) of the intragenic microsatellite D13S232. Unexpectedly, this allele is most frequent in the Caucasian population but not in the normal Gypsy population. The clinical severity of all patients demonstrates that the C283Y missense mutation in a homozygous state causes a severe LGMD2C (DMD-like). The elevated number of families ascertained let us assume that LGMD2C is prevalent in the Gypsy population, and that all the families have inherited a founding mutation.

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β–sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex

Cited by 406 publications

References 44 publications

Noninvasive monitoring of therapeutic gene transfer in animal models of muscular dystrophies

Noninvasive monitoring of therapeutic gene transfer in animal models of muscular dystrophies

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

Severe limb girdle muscular dystrophy in Spanish gypsies: further evidence for a founder mutation in the γ-sarcoglycan gene

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