Mutations in GJC2 (Cx47), expressed in oligodendrocytes cause three disorders: a severe early onset dysmyelinating disorder, Pelizaeus-Merzbacher-Like disease (PMLD1 or HLD2); hereditary spastic paraplegia (SPG44), which has a milder phenotype and later onset; and a subclinical leukodystrophy.
Recessive mutations in the Gap Junction Protein Gamma 2 (GJC2) gene cause Pelizaeus-Merzbacher-like disease type 1, a severe infantile-onset hypomyelinating leukodystrophy.
The restrictive permeability of Cx47 channels and the diffusion barrier of Cx47-Cx43 channels was abolished by a mutation associated with leukodystrophy, the Cx47P90S, suggesting a novel pathogenic mechanism underlying myelin disorders that involves alterations in the panglial permeation.
Pelizaeus-Merzbacher-like disease or hypomyelinating leukodystrophy-2 is an autosomal recessively inherited leukodystrophy with childhood onset resulting from mutations in the gene encoding the gap junction protein connexin 47 (Cx47, encoded by GJC2).
Furthermore, mutations in the GJA12/GJC2 gene encoding the gap junction protein Cx47, which is expressed in oligodendrocytes, have been identified in families with progressive leukodystrophy, known as Pelizaeus-Merzbacher-like disease, as well as in patients with hereditary spastic paraplegia.