Understanding CMT1X/CMTX1 and GJB1

CMT1X (also called CMTX1) is the most common form of CMTX and the second most common form of CMT overall, after CMT1A, accounting for 7-18% of all CMT cases. CMT1X is caused by mutations in the GJB1 (Gap Junction β-1) gene. The GJB1 gene contains the genetic code for a protein called connexin 32 (Cx32), which is normally situated in cell membranes in a number of tissues, including in the myelinating Schwann cells of the peripheral nervous system.

Connexin 32 proteins form groupings called connexons, or hemichannels. These hemichannels span across cell membranes and allow various molecules, including simple ions and signaling molecules, to pass between the inside and outside of the cell.

In addition, hemichannels in one cell membrane can dock with hemichannels in another nearby membrane to form connexon channels. This can create connections between different cells, or in the case of myelinating Schwann cells, connections between different parts of the same cell. These points of connection allow communication between the layers of Schwann cells in areas called paranodal loops. (Although not shown in the illustration below, this also occurs in another specialized area of the Schwann cell called Schmidt-Lanterman incisures.)

Hemichannels are also thought to have important functions in mitochondria, specialized structures that allow cells to use energy.