DMD

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 costamere or the dystrophin-associated protein complex.

The dystrophin-associated protein complex is a multiprotein complex that includes dystrophin and the dystrophin-associated proteins. Many muscle proteins, such as α-dystrobrevin, syncoilin, synemin, sarcoglycan, dystroglycan, and sarcospan, colocalize with dystrophin at the costamere.

As of 2007, dystrophin is the longest gene known, covering 2.4 megabases (0.08% of the human genome) at locus Xp21. The primary transcript measures about 2,400 kilobases and takes 16 hours to transcribe, the mature mRNA measures 14.0 kilobases. The 79 exons code for a protein of over 3500 amino acid residues.

Function

 The dystrophin complex has two functions: a structural role in maintaining sarcolemmal integrity during contraction and a scaffolding function that recruits signaling proteins such as neuronal nitric oxide synthase to the membrane.

Gene

 this large gene consists of 79 exons and 8 promoters spread over 2.2 million base pairs of genomic DNA.

Features

 dystrophin-glycoprotein complex

Pathology

Dystrophin-associated muscular dystrophies range from the severe Duchenne muscular dystrophy (DMD) (MIM.310200) to the milder Becker muscular dystrophy (BMD; MIM.300376).

Its deficiency is one of the root causes of muscular dystrophy. It was first identified in 1987 by Louis M. Kunkel, after the 1986 discovery of the mutated gene that causes Duchenne muscular dystrophy (DMD).

Normal tissue contains small amounts of dystrophin (about 0.002% of total muscle protein), but its absence leads to both DMD and fibrosis, a condition of muscle hardening. A different mutation of the same gene causes defective dystrophin, leading to Becker’s muscular dystrophy (BMD).

Though its role in airway smooth muscle is not well established recent research indicates that dystrophin along with other subunits of dystrophin glycoprotein complex is associated with phenotype maturation.

 mutations in Duchenne muscular dystrophy (DMD)
 mutations in Becker muscular dystrophy (BMD)
(deletions of one or more exons account for 55%-65% of cases of DMD and BMD)

 mutations in X-linked dilated cardiomyopathy