Next-generation sequencing identified a novel PLP1 deletion in a proband with connatal pelizaeus-merzbacher disease

Pelizaeus-Merzbacher disease (PMD; MIM #312080) is a rare X-linked recessive disorder characterized with early nystagmus, hypotonia, ataxia and neurodegeneration. PMD is caused by mutations in PLP1 gene that encodes for the myelin protein Proteolipid Protein 1 (PLP1) and the spliced variant DM20. Generally, patients with PLP1 missense mutations show the most severe form of PMD (connatal form), whereas PLP1 duplications, that are the most common mutations result in the classical PMD. Deletions and null mutations are associated to the mild form of PMD and Hereditary Spastic Paraplegia type 2 (SPG2). The present paper shows a boy of 17-year-old with clinical diagnosis of PMD in which we found a novel PLP1 deletion using Next Generation Sequencing (NGS). Clinical exome sequencing was performed on the affected proband as well as his mother. Sequencing results suggested of a complete or partial deletion of PLP1 gene. MLPA (Multiplex Ligation-dependent Probe Amplification) analysis confirmed a deletion in exon 6 of PLP1 inherited from asymptomatic carrier mother. In conclusions, although the patient we described had a severe but stable phenotype, even if he present a deletion in PLP1, suggesting that also deletions give rise to variable phentotypes of PMD. This report also extends the spectrum of PLP1 mutations and highlights the diagnostic utility of NGS to investigate complex clinical phenotypes.