Gamma-sarcoglycan is a
protein that in humans is encoded by the SGCGgene.[5][6] The α to δ-sarcoglycans are expressed predominantly (β) or exclusively (α, γ and δ) in
striated muscle.[7] A
mutation in any of the
sarcoglycan genes may lead to a secondary deficiency of the other sarcoglycan proteins, presumably due to destabilisation of the sarcoglycan complex.[8] The disease-causing mutations in the α to δ genes cause disruptions within the
dystrophin-associated protein (DAP) complex in the
muscle cell membrane.[9] The transmembrane components of the DAP complex link the
cytoskeleton to the
extracellular matrix in adult
muscle fibres,[10] and are essential for the preservation of the integrity of the muscle cell membrane.[11]
Function
Gamma-sarcoglycan is one of several sarcolemmal transmembrane glycoproteins that interact with
dystrophin, probably to provide a link between the membrane associated cytoskeleton and the extracellular matrix. Defects in the protein can lead to early onset autosomal recessive muscular dystrophy, in particular
limb-girdle muscular dystrophy, type 2C (LGMD2C).[6]
Structure
Gene
Human SGCG gene maps to
chromosome 13 at q12, spans over 100 kb of DNA and includes 8
exons.[12]
Sarcoglycanopathies are autosomal recessive
limb girdle muscular dystrophies (LGMDs) caused by mutations in any of the four sarcoglycan genes: α (LGMD2D), β (LGMD2E), γ (LGMD2C) and δ (LGMD2F).[7] Severe childhood autosomal recessive muscular dystrophy (SCARMD) is a progressive muscle-wasting disorder that segregates with microsatellite markers at γ-sarcoglycan gene. Mutations in the γ-sarcoglycan gene were first described in the
Maghreb countries of North Africa,[13] where γ-sarcoglycanopathy has a higher than usual incidence. One common mutation, Δ-521T, which causes a severe phenotype, occurs both in the Maghreb population and in other countries.[12] A Cys283Tyr mutation has been identified in the
Gypsy population causing a severe phenotype and a Leu193Ser mutation which causes a mild phenotype.[5][14]
^
abNoguchi S, McNally EM, Ben Othmane K, Hagiwara Y, Mizuno Y, Yoshida M, Yamamoto H, Bönnemann CG, Gussoni E, Denton PH, Kyriakides T, Middleton L, Hentati F, Ben Hamida M, Nonaka I, Vance JM, Kunkel LM, Ozawa E (Nov 1995). "Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy". Science. 270 (5237): 819–22.
Bibcode:
1995Sci...270..819N.
doi:
10.1126/science.270.5237.819.
PMID7481775.
S2CID84713401.
^
abNowak KJ, Walsh P, Jacob RL, Johnsen RD, Peverall J, McNally EM, Wilton SD, Kakulas BA, Laing NG (Feb 2000). "Severe gamma-sarcoglycanopathy caused by a novel missense mutation and a large deletion". Neuromuscular Disorders. 10 (2): 100–7.
doi:
10.1016/s0960-8966(99)00063-2.
PMID10714584.
S2CID54410727.
^van der Kooi AJ, de Visser M, van Meegen M, Ginjaar HB, van Essen AJ, Jennekens FG, Jongen PJ, Leschot NJ, Bolhuis PA (Jun 1998). "A novel gamma-sarcoglycan mutation causing childhood onset, slowly progressive limb girdle muscular dystrophy". Neuromuscular Disorders. 8 (5): 305–8.
doi:
10.1016/s0960-8966(98)00040-6.
PMID9673983.
S2CID33437157.
^Guyon JR, Kudryashova E, Potts A, Dalkilic I, Brosius MA, Thompson TG, Beckmann JS, Kunkel LM, Spencer MJ (October 2003). "Calpain 3 cleaves filamin C and regulates its ability to interact with gamma- and delta-sarcoglycans". Muscle Nerve. 28 (4): 472–83.
doi:
10.1002/mus.10465.
PMID14506720.
S2CID86353802.
Noguchi S, McNally EM, Ben Othmane K, Hagiwara Y, Mizuno Y, Yoshida M, Yamamoto H, Bönnemann CG, Gussoni E, Denton PH, Kyriakides T, Middleton L, Hentati F, Ben Hamida M, Nonaka I, Vance JM, Kunkel LM, Ozawa E (1995). "Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy". Science. 270 (5237): 819–22.
Bibcode:
1995Sci...270..819N.
doi:
10.1126/science.270.5237.819.
PMID7481775.
S2CID84713401.
Vermeer S, Verrips A, Willemsen MA, ter Laak HJ, Ginjaar IB, Hamel BC (2004). "Novel mutations in three patients with LGMD2C with phenotypic differences". Pediatr. Neurol. 30 (4): 291–4.
doi:
10.1016/j.pediatrneurol.2003.11.006.
PMID15087111.
Gamma-sarcoglycan is a
protein that in humans is encoded by the SGCGgene.[5][6] The α to δ-sarcoglycans are expressed predominantly (β) or exclusively (α, γ and δ) in
striated muscle.[7] A
mutation in any of the
sarcoglycan genes may lead to a secondary deficiency of the other sarcoglycan proteins, presumably due to destabilisation of the sarcoglycan complex.[8] The disease-causing mutations in the α to δ genes cause disruptions within the
dystrophin-associated protein (DAP) complex in the
muscle cell membrane.[9] The transmembrane components of the DAP complex link the
cytoskeleton to the
extracellular matrix in adult
muscle fibres,[10] and are essential for the preservation of the integrity of the muscle cell membrane.[11]
Function
Gamma-sarcoglycan is one of several sarcolemmal transmembrane glycoproteins that interact with
dystrophin, probably to provide a link between the membrane associated cytoskeleton and the extracellular matrix. Defects in the protein can lead to early onset autosomal recessive muscular dystrophy, in particular
limb-girdle muscular dystrophy, type 2C (LGMD2C).[6]
Structure
Gene
Human SGCG gene maps to
chromosome 13 at q12, spans over 100 kb of DNA and includes 8
exons.[12]
Sarcoglycanopathies are autosomal recessive
limb girdle muscular dystrophies (LGMDs) caused by mutations in any of the four sarcoglycan genes: α (LGMD2D), β (LGMD2E), γ (LGMD2C) and δ (LGMD2F).[7] Severe childhood autosomal recessive muscular dystrophy (SCARMD) is a progressive muscle-wasting disorder that segregates with microsatellite markers at γ-sarcoglycan gene. Mutations in the γ-sarcoglycan gene were first described in the
Maghreb countries of North Africa,[13] where γ-sarcoglycanopathy has a higher than usual incidence. One common mutation, Δ-521T, which causes a severe phenotype, occurs both in the Maghreb population and in other countries.[12] A Cys283Tyr mutation has been identified in the
Gypsy population causing a severe phenotype and a Leu193Ser mutation which causes a mild phenotype.[5][14]
^
abNoguchi S, McNally EM, Ben Othmane K, Hagiwara Y, Mizuno Y, Yoshida M, Yamamoto H, Bönnemann CG, Gussoni E, Denton PH, Kyriakides T, Middleton L, Hentati F, Ben Hamida M, Nonaka I, Vance JM, Kunkel LM, Ozawa E (Nov 1995). "Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy". Science. 270 (5237): 819–22.
Bibcode:
1995Sci...270..819N.
doi:
10.1126/science.270.5237.819.
PMID7481775.
S2CID84713401.
^
abNowak KJ, Walsh P, Jacob RL, Johnsen RD, Peverall J, McNally EM, Wilton SD, Kakulas BA, Laing NG (Feb 2000). "Severe gamma-sarcoglycanopathy caused by a novel missense mutation and a large deletion". Neuromuscular Disorders. 10 (2): 100–7.
doi:
10.1016/s0960-8966(99)00063-2.
PMID10714584.
S2CID54410727.
^van der Kooi AJ, de Visser M, van Meegen M, Ginjaar HB, van Essen AJ, Jennekens FG, Jongen PJ, Leschot NJ, Bolhuis PA (Jun 1998). "A novel gamma-sarcoglycan mutation causing childhood onset, slowly progressive limb girdle muscular dystrophy". Neuromuscular Disorders. 8 (5): 305–8.
doi:
10.1016/s0960-8966(98)00040-6.
PMID9673983.
S2CID33437157.
^Guyon JR, Kudryashova E, Potts A, Dalkilic I, Brosius MA, Thompson TG, Beckmann JS, Kunkel LM, Spencer MJ (October 2003). "Calpain 3 cleaves filamin C and regulates its ability to interact with gamma- and delta-sarcoglycans". Muscle Nerve. 28 (4): 472–83.
doi:
10.1002/mus.10465.
PMID14506720.
S2CID86353802.
Noguchi S, McNally EM, Ben Othmane K, Hagiwara Y, Mizuno Y, Yoshida M, Yamamoto H, Bönnemann CG, Gussoni E, Denton PH, Kyriakides T, Middleton L, Hentati F, Ben Hamida M, Nonaka I, Vance JM, Kunkel LM, Ozawa E (1995). "Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy". Science. 270 (5237): 819–22.
Bibcode:
1995Sci...270..819N.
doi:
10.1126/science.270.5237.819.
PMID7481775.
S2CID84713401.
Vermeer S, Verrips A, Willemsen MA, ter Laak HJ, Ginjaar IB, Hamel BC (2004). "Novel mutations in three patients with LGMD2C with phenotypic differences". Pediatr. Neurol. 30 (4): 291–4.
doi:
10.1016/j.pediatrneurol.2003.11.006.
PMID15087111.