Different mutations in the same codon of the proteolipid protein gene, PLP, may help in correlating genotype with phenotype in Pelizaeus-Merzbacher disease/X-linked spastic paraplegia (PMD/SPG2).
Investigating 82 strictly selected sporadic cases of PMD, we found PLP mutations in 77%; complete PLP-gene duplications were the most frequent abnormality (62%), whereas point mutations in coding or splice-site regions of the gene were involved less frequently (38%).
A duplication of the whole PLP gene is the most common mutation and results usually in the milder classical phenotype, whereas point mutations in PLP gene often result in the rarer and more severe connatal form of PMD.
Mutation c.453_453+6del7insA affects the exon 3B donor splice site and disrupts the PLP1-transcript without affecting the DM20, was found in a patient with severe Pelizaeus-Merzbacher disease and in his female cousin with early-onset spastic paraparesis.
Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive hypomyelination disorder caused by mutations in the proteolipid protein 1 gene (<i>PLP1</i>) located on chromosome Xq22.
We detected a novel pathogenic PLP1 missense mutation c.251C > A (p.Ala84Asp) allowing us to make a diagnosis of Pelizaeus-Merzbacher Disease for this family.