The Cx26-G59S mutation, associated with mutilating keratoderma, ichthyosis, and congenital deafness, likely disrupts Cx26 transport and hemichannel permeability, potentially contributing to the pathogenesis of VS as alterations in the first extracellular domain have been shown to affect Cx26 transport and hemichannel permeability. The gene discussed is GJB2; the disease is Palmoplantar keratoderma.