Sarcoglycan, Gamma

Alternative Names

  • SGCG
  • Dystrophin-Associated Glycoprotein, 35-KD
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OMIM Number

608896

NCBI Gene ID

6445

Uniprot ID

Q13326

Length

164,660 bases

No. of Exons

10

No. of isoforms

1

Protein Name

Gamma-sarcoglycan

Molecular Mass

32379 Da

Amino Acid Count

291

Genomic Location

chr13:23,160,506-23,325,165

Gene Map Locus
13q12.12

Description

Sarcoglycans are a family of membrane glycoproteins that associate to form the sarcoglycan protein complex, which is responsible for connecting the muscle fiber cytoskeleton to the extracellular matrix, thereby affording support and stability to the muscles. Gamma sarcoglycan is one of the proteins in this complex. The sarcoglycan complex, in fact is made up of two distinct sub-complexes, and the gamma sarcoglycan protein is an integral part of both these sub-complexes. Incidentally, SGCG interacts with the Filamin Gamma (FLNC) component of the sarcoglycan complex. This complex itself, interacts with other proteins like dystrophins, dystrophin associated glycoproteins, and dystroglycans to form the dystrophin-glycoprotein complex, which in turn functions to bind actin to the extracellular matrix of myocytes.

In patients with Limb Girdle Muscular Dystrophy, Type 2C, gamma sarcoglycan is absent from the myocyte membranes, thereby explaining the physiology of the disease.

Molecular Genetics

The SGCG gene is located on chromosome 13, where it spans a length of just over 144 kb with its eight exons. Of these, exon 1 encompasses the 5' untranslated region, whereas exon 8 includes the 3' UTR. The gamma sarcoglycan protein, on the other hand, is made up of 291 amino acids and weighs about 32 KDa. The protein is a type II transmembrane protein, and consists of the typical extracellular, transmembrane, and intracellular domains. The C-terminal extracellular domain (233 residues) contains four conserved Cysteine residues as well as an Asparagine-linked glycosylation site. There is a single transmembrane domain, which consists of 21 amino acid residues. The N-terminal intracellular domain (37 amino acids) lacks a signal sequence, but consists of charged residues (RKR) from position 32 to 34.

As mentioned above, mutations in the SGCG gene lead to the development of LGMD2C. The most frequently occurring mutation amongst the European Gypsy population affected with this disease is a Cys283Tyr missense mutation. In the Northern African populations, on the other hand, the 525delT mutation is much more common in affected individuals.

Epidemiology in the Arab World

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Other Reports

Lebanon

Nair et al. 2018 described a patient with muscular dystrophy and mildly elevated creatinine kinase. The patient exhbited an exon 7 deletion in the sarcoglycan gamma gene. 

Morocco

Vermeer et al. (2004) described a Moroccan patient who presented with progressive walking disturbances for several years, exercise intolerance, and leg pains. Muscle biopsy revealed reduced expression of the sarcoglycans. Mutation screening of the SGCG gene identified a novel nonsense mutation in this patient: G93A (Trp31X) on exon 2. The patient was homozygous for this mutation.

Tunisia

In 2 affected sibs from a Tunisian family with limb-girdle muscular dystrophy 2C reported by Ben Othmane et al. (1992), Noguchi et al. (1995) identified a homozygous 1-bp deletion in the SGCG gene (which they designated 645delT). The same mutation was found in affected members of 2 additional Tunisian SCARMD families. The deletion changed the reading frame at codon 175, creating a premature stop signal at codon 193 and loss of a cluster of cysteine residues in the distal portion of the protein. Immunostaining of 1 patient's muscle showed a deficiency of alpha-, beta-, and gamma-sarcoglycan, indicating instability of the entire dystrophin-glycoprotein complex.

Fendri et al. (2006) described a 21-year old Tunisian male, born to consanguineous parents, who was diagnosed with limb girdle muscular dystrophy. A homozygous haplotype was revealed for this patient upon linkage analysis with markers spanning the SGCG locus. Upon mutation screening, a homozygous del521T mutation was identified in the SGCG gene in this patient. One of his healthy siblings was also found to be heterozygous for this mutation.

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