Mutation analysis of the M6b gene in patients with Pelizaeus-Merzbacher-Like syndrome

Pelizaeus-Merzbacher-like syndrome is an undetermined leukodystrophy disorder of diffuse hypomyelination. The patients' clinical phenotype is indistinguishable from classical Pelizaeus-Merzbacher disease (PMD), but the patients lack PLP1 gene duplications or mutations. They represent about 20% of all cases with a clinical PMD phenotype. The M6b gene has been localized to Xp22.2. The encoded M6B protein is a member of a novel proteolipid family that also includes other major brain myelin components like the proteolipid protein (PLP). Recent cotransfection experiments suggest a protein-protein interaction of M6B and mutant PLP1 that may contribute to oligodendrocyte dysfunction in PMD. Therefore, M6b has been considered a good candidate gene for Pelizacus-Merzbacher-like syndrome. However, our molecular analyses in eight thoroughly characterized patients make it unlikely that mutations in this gene are involved in this subgroup of human hypomyelination disorders. (C) 2004 Wiley-Liss, Inc.