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 Pelizaeus-Merzbacher disease. Therefore, M6b has been considered a good candidate gene for Pelizaeus-Merzbacher-like syndrome. Eight thoroughly characterized patients with Pelizaeus-Merzbacher-like syndrome included in the German network for unknown leukoencephalopathies were investigated for mutations in coding and splice site regions of the M6b gene as well as for gene duplication and no abnormalities have been found. Although mutations in the M6b gene are not the primary cause for the analysed subgroup of human hypomyelination disorders the gene still remains a good candidate for neurological disorders that involve brain myelin and map to the X-chromosome at Xp22.2.

Keywords: leukodystrophy; hypomyelination; M6b gene; PLP1 gene; Pelizaeus-Merzbacher-like syndrome