Identification and functional study of novel PLP1 mutations in Chinese patients with Pelizaeus-Merzbacher disease

Purpose: Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive hypomyelination disorder characterized by nystagmus, ataxia, impaired motor development, and progressive spasticity. Identification of proteolipid protein 1 (PLP1) mutations in Chinese patients with Pelizaeus-Merzbacher disease (PMD) and confirmation of the biological impacts of the identified mutations are the aims of this study.

Methods: An analysis of clinical materials and a follow-up study were conducted for the patients with PMD. Sequencing and immunofluorescence were applied for molecular analysis of the causative gene PLP1.

Results: We identified PLP1 mutations in seven male patients with PMD. Three novel missense mutations (c.353C>G, p.T118R; c.623G>T, p.G208V; c.709T>G, p.F237V) and three reported missense mutations (c.467C>T, p.T156I; c.517C>T, p.P173S; c.646C>T, p.P216S) of PLP1 were identified from seven Chinese PMD patients. The three mutations (F237V in patient 2, P216S in patient 5 and T156I in patient 6) were de novo. Mutant proteins were trapped in the lumen of endoplasmic reticulum.

Conclusion: We have identified six pathogenic mutations, enriching the specific spectrum of missense mutations in the patients with PMD. The six PLP1 mutations are probably pathogenic. By reviewing the known PLP1 mutations, we have preliminarily revealed the position of missense mutation may be associated with the severity of PMD.