There’s Pelizaeus-Merzbacher disease, and then there’s Pelizaeus-Merzbacher-like disease

Thanks to the esteemed Dr. Mark Cohen of Case Western Reserve University, who sent me a recently published article entitled: GJA12 mutations are a rare cause of Pelizaeus-Merzbacher-like disease (Henneke M, et al. Neurology 2008;70;748-754). The plain old form of Pelizaeus-Merzbacher disease, the prototypical hypomyelinating leukodystrophy secondary to an inborn error of myelin formation, is caused by a mutation in the proteolipid protein 1 (PLP1) gene on the X chromosome. But Pelizaeus-Merzbacher-like disease differs from the classical form in being associated with a mutation other than PLP1. One genetic substrate of PMLD was first described by Dr. Jutta Gartner’s group in Goettingen, Germany as having an autosomal recessive inheritance pattern associated with mutation in gap junction protein alpha-12 (GJA12). In this study, the Gartner group looked at 193 patients with PMLD and found that only 8.3% of them carried the GJA12 mutation. Finally, the authors write: “The clinical phenotype of patients with a GJA12 mutation was evaluated and is overall comparable to the clinical features seen in mild forms of proteolipid protein 1(PLP1) related disorder but with better cognition and earlier signs of axonal degeneration.” Thanks again for the article, Mark!