Autosomal recessive limbgirdle muscular dystrophy, LGMD2F, is caused by a mutation in the δ–sarcoglycan gene

Abstract

Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of inherited neuromuscular disorders characterized by proximal muscular weakness of the pelvic and shoulder girdles and a variable progression with symptoms, ranging from very severe to mild. One autosomal dominant (LGMD1A, at chromosome 5q22.3-31.3) (ref. 3) and five autosomal recessive (AR) loci responsible for this phenotype have been identified: LGMD2A at 15q (ref. 4); LGMD2B at 2p (ref. 5), LGMD2C at 13q (ref. 6), LGMD2D at 17q (ref. 7) and LGMD2E at 4q (refs 8,9). In the muscle membrane, dystrophin associates with several proteins and glycoproteins organized in two main subcomplexes: the dystroglycan (DG) and sarcoglycan (SG) complexes. The genes for LGMD2C, LGMD2D and LGMD2E code for proteins of the SG complex. We recently mapped a sixth AR form of LGMD, LGMD2F, to chromosome 5q33-34 in two Brazilian families. In the same chromosomal interval we also mapped the delta SG gene, encoding a novel 35-kD component of the sarcoglycan (SG) complex. We now show that a homozygous mutation in the delta SG gene (a single nucleotide deletion that alters its reading frame) is the cause of LGMD2F.

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).…”

Limb-girdle muscular dystrophy 2I: phenotypic variability within a large consanguineous Bedouin family associated with a novel FKRP mutation

“…LGMD2A (CAPN3 at 15q15.1), 2,3 LGMD2B (DYSF at 2p12 -16), 4,5 LGMD2C (SGCG at 13q12), 6,7 LGMD2D (ADL at 17q12 -q21.33), 8 -10 LGMD2E (SGCB at 4q12), 11,12 LGMD2F (SGCD at 5q33 -34), 13,14 LGMD2G (TCAP at 17q11 -q12), 1,15 LGMD2H (TRIM32 at 9q31 -q34.1), 16,17 LGMD2I (FKRP at 19q13.3), 18,19 and LGMD2J (TTN at 2q31). 20 The involved genes encode either structural components of muscle, that is, g-, a-, b-, and d-sarcoglycans, responsible for LGMD2C to 2F, respectively, or proteins of other functions.…”