The sarcoglycanopathies are a collection of diseases resulting from

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA replication, DNA or viral repl ...

s in any of the five

sarcoglycan The sarcoglycans are a family of transmembrane proteins (α, β, γ, δ or ε) involved in the protein complex responsible for connecting the muscle fibre cytoskeleton to the extracellular matrix, preventing damage to the muscle fibre sarcolemma t ...

genes: α, β, γ, δ or ε. The five sarcoglycanopathies are: α-sarcoglycanopathy, LGMD2D; β-sarcoglycanopathy, LGMD2E; γ-sarcoglycanopathy, LGMD2C; δ-sarcoglycanopathy, LGMD2F and ε-sarcoglycanopathy, myoclonic dystonia. The four different sarcoglycan genes encode proteins that form a

tetramer A tetramer () ('' tetra-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula ...

ic complex at the muscle cell plasma membrane. This complex stabilizes the association of

dystrophin Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the cost ...

with the

dystroglycan Dystroglycan is a protein that in humans is encoded by the ''DAG1'' gene. Dystroglycan is one of the dystrophin-associated glycoproteins, which is encoded by a 5.5 kb transcript in ''Homo sapiens'' on chromosome 3. There are two exons that are s ...

s and contributes to the stability of the plasma membrane

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is com ...

. The four sarcoglycan genes are related to each other structurally and functionally, but each has a distinct

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

location. In outbred populations, the relative frequency of mutations in the four genes is alpha >> beta >> gamma >> delta in an 8:4:2:1 ratio. No common mutations have been identified in outbred populations except the R77C mutation, which accounts for up to one-third of the mutated SGCA

allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...

s. Founder mutations have been observed in certain populations. A 1997 Italian clinical study demonstrated variations in muscular dystrophy progression dependent on the sarcoglycan gene affected.

References

{{Reflist Muscular disorders