NEFL

The NEFL gene provides instructions for making the smallest protein component (the light subunit) of neurofilaments. Neurofilaments, which are assembled from light, medium, and heavy subunits, are essential for normal nerve function. They form a structural framework that helps to define the shape and size of nerve cells. Cross-linking or bridging between neurofilaments maintains the diameter of the fiber, or axon, that extends from a nerve cell. Maintaining the proper axon diameter is essential for the transmission of nerve impulses.

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

Researchers have identified more than 10 NEFL mutations that cause forms of Charcot-Marie-Tooth disease known as type 1F and type 2E. Most NEFL mutations replace one of the protein building blocks (amino acids) in the neurofilament light subunit with an incorrect amino acid. Some mutations delete or duplicate part of the NEFL gene, which alters the instructions for making the neurofilament light subunit. NEFL mutations probably alter the size or shape of neurofilament light subunits.

Altered neurofilament light subunits likely disrupt the assembly of neurofilaments or their transport to the axon. These disruptions may cause abnormalities in axons and impair the transmission of nerve impulses. Axonal abnormalities are a sign of type 2E Charcot-Marie-Tooth disease. In some cases, the speed of nerve transmission is reduced, which is a sign of type 1F Charcot-Marie-Tooth disease.