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 Pelizaeus-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.