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 or viral replication, m ...
s in any of the five
sarcoglycan 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 T ...
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 cos ...
with the
dystroglycans 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 comp ...
. 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 ar ...
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
Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily af ...
progression dependent on the sarcoglycan gene affected.
References
{{Reflist
Muscular disorders