Analyses of the presence of mutations in Dystrophin protein to predict their relative influences in the onset of Duchenne Muscular Dystrophy

Cell Signal. 2014 Dec;26(12):2857-64. doi: 10.1016/j.cellsig.2014.09.006. Epub 2014 Sep 16.

Abstract

Muscle plays a vital role in the life of vertebrates like humans. Muscle contraction is the only criterion required for locomotion. Muscle fibers also play a vital role as the provider of mechanical strength and act as a large repository of building blocks for protein synthesis in living beings. Muscles function as per the messages received from the extra-cellular signals. One of the central players responsible for capturing and transmission of extra-cellular signals to maintain the integrity of muscle function is the protein called Dystrophin (Dp). However, the wild type Dp protein accumulates some mutations which lead to a severe disease called Duchenne Muscular Dystrophy (DMD). The disease is so frequent that it is known to affect 1 in 3500 newborns per year. There are a number of reports that identify the mutations leading to DMD. Interestingly, it is also observed that the type of mutations affects the severity of the disease. But the biochemical mechanism of the DMD onset is still obscure. In the present scenario, an attempt has been made to analyze the mutations in the development of the disease. We analyzed the changes in secondary structure, solvent accessibility and stability of the Dp protein associated with the mutations. We tried to correlate the type of mutations with the severity of the disease. So far this is the first report that deals with the analyses of the mutations leading to DMD. This study would therefore be essential to come up with a plausible mechanism of DMD disease onset.

Keywords: Duchenne Muscular Dystrophy; Dystrophin protein; Mode of DMD onset; Pathogenic mutations; Severity of mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Amino Acid Sequence
  • Animals
  • Conserved Sequence
  • Databases, Genetic
  • Dystrophin / chemistry
  • Dystrophin / genetics*
  • Humans
  • Molecular Sequence Data
  • Muscular Dystrophy, Duchenne / genetics*
  • Mutation / genetics*
  • Phylogeny
  • Protein Binding
  • Protein Structure, Tertiary
  • Repetitive Sequences, Amino Acid

Substances

  • Actins
  • Dystrophin