Mutations in the Dystrophin-Associated Protein γ-Sarcoglycan in Chromosome 13 Muscular Dystrophy

Abstract

Severe childhood autosomal recessive muscular dystrophy (SCARMD) is a progressive muscle-wasting disorder common in North Africa that segregates with microsatellite markers at chromosome 13q12. Here, it is shown that a mutation in the gene encoding the 35-kilodalton dystrophin-associated glycoprotein, gamma-sarcoglycan, is likely to be the primary genetic defect in this disorder. The human gamma-sarcoglycan gene was mapped to chromosome 13q12, and deletions that alter its reading frame were identified in three families and one of four sporadic cases of SCARMD. These mutations not only affect gamma-sarcoglycan but also disrupt the integrity of the entire sarcoglycan complex.

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

“…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.…”

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

“…[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).…”

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

“…Peptides were purified by reverse-phase HPLC and subjected to amino acid sequencing by Edman degradation. Eight different peptide sequences were obtained and during the process of preparing this manuscript for publication, Noguchi et al [17] reported the primary structure of y-sarcoglycan. All the peptide sequences that we obtained were found in the reported amino acid sequence of y-sarcoglycan.…”

“…IFEBS Letters 381 (1996) [15][16][17][18][19][20] the N-terminus. These synthetic peptides were conjugated through the N-terminal cysteine to keyhole limpet hemocyanin (Pierce Chemical Co) using m-maleimidobenzoic acid/N-hydroxysuccinimide ester (Pierce Chemical Co.) as described [33], mixed with Freund's adjuvant and injected to sheep.…”

“…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.…”