EGR2

The EGR2 gene provides instructions for making a protein called early growth response 2, which is part of the early growth response family of proteins. These proteins bind to specific areas of DNA and help control the activity of particular genes. On the basis of this action, the proteins are referred to as transcription factors.

The early growth response 2 protein activates several genes that are involved in the formation and maintenance of myelin, the fatty substance that covers and protects nerve cells. Myelin promotes the efficient transmission of nerve impulses. If myelin is lost (demyelination) or its structure is disrupted, the transmission of nerve impulses is impaired.

Charcot-Marie-Tooth disease - caused by mutations in the EGR2 gene

Mutations in the EGR2 gene can cause two forms of Charcot-Marie-Tooth disease, type 1D or type 4E (sometimes called congenital hypomyelinating neuropathy). These mutations replace one of the protein building blocks (amino acids) used to make early growth response 2 with an incorrect amino acid. As a result, the altered protein cannot bind effectively to DNA, which disrupts the control of genes involved in myelin formation and maintenance. This disruption impairs the transmission of nerve impulses, leading to the symptoms of Charcot-Marie-Tooth disease.

A particular mutation has been identified in individuals with type 1D Charcot-Marie-Tooth disease who also have hearing loss. As a result of this mutation, the amino acid arginine is replaced with the amino acid histidine at protein position 381 (written as Arg381His). Other EGR2 mutations cause a severe form of type 1D (sometimes called Dejerine-Sottas syndrome) that begins during infancy or early childhood. As a result of these mutations, the amino acid arginine is replaced by the amino acid tryptophan at protein position 359 (written as Arg359Trp) or the amino acid aspartic acid is replaced by the amino acid tryptophan at protein position 383 (Asp383Tyr). Researchers do not yet understand why these particular mutations cause severe symptoms that begin early in life.