Pelizaeus-Merzbacher-like disease (PMLD) and hereditary spastic paraplegia 44 (SPG44) are caused by mutations in both copies of the GJC2 gene (autosomal recessive inheritance). This gene encodes a protein called connexin 47. These connexin proteins form channels in membranes of the cells of the nervous system and are responsible for communication between them. Defects in connexin47 impair myelin formation in the brain. Myelin forms multiple layers that ensheath nerve cells and their long processes called axons (the "wires" of the nervous system). Myelin sheaths insulate axons and increases the velocity of the electrical impulses travelling along the axons at its entire length. Thus, the rapid transmission of electrical impulses between nerve cells is impaired in these patients.
Hereditary lymphedema type 1C (LMPH1C) is caused by mutations in only one copy of the GJC2gene (autosomal dominant inheritance), but it is unclear what role the GJC2gene plays in the lymphatic system and how exactly mutations cause this condition. Ferrell et al. (2010) hypothed that the mutations might result in impaired channel activity, which could in the end impair the directionality of lymphatic flow.
GJC2