Mutations in the PLP1 gene residue p. Gly198 as the molecular basis of Pelizeaus-Merzbacher phenotype.

Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2 (SPG2) are rare X-linked allelic disorders caused by mutations in the PLP1 gene, encoding the main component of myelin, proteolipid protein 1 (PLP1). Various types of mutations, acting through different molecular mechanism, cause the diseases. Duplications of variable size at Xq22.2, containing the entire PLP1, are responsible for more than 50% of PMD cases. Other causes of PMD include point mutations, gene deletions and triplications. There is a spectrum of PLP1-related disorders with some correlation between the type of mutation and phenotype. Generally the missense mutations cause the more severe forms of the disease, the most common PLP1 duplications, result in the classical PMD whereas deletions and null mutations in mild form of PMD and SPG2. We present a patient with c.593G>A substitution in the exon 4 of the PLP1 gene causing a novel missense mutation p.Gly198Asp, finally diagnosed as PMD but showing an atypical MRI picture.