title: Identification and functional study of novel PLP1 mutations in Chinese patients with Pelizaeus-Merzbacher disease.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, 100034 Beijing, China.
authors.forename: Han
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Pediatrics, Peking University First Hospital, 100034 Beijing, China; Department of Neurology, Xi'an North Hospital, 710043 Xi'an, Shaanxi, China.
authors.forename: Hongchun
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Pediatrics, Peking University First Hospital, 100034 Beijing, China; Department of Neurology, Shanxi Medical University First Hospital, 030001 Taiyuan, Shanxi, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of Pediatrics, Peking University First Hospital, 100034 Beijing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, Peking University First Hospital, 100034 Beijing, China; Department of Neurology, Shanxi Medical University First Hospital, 030001 Taiyuan, Shanxi, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Kou
authors.affiliation: Department of Pediatrics, Peking University First Hospital, 100034 Beijing, China.
authors.forename: Dongxiao
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Peking University First Hospital, 100034 Beijing, China.
authors.forename: Haoran
authors.initials: H
authors.lastname: Ji
authors.affiliation: Department of Pediatrics, Peking University First Hospital, 100034 Beijing, China.
authors.forename: Xiru
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Neurology, Shanxi Medical University First Hospital, 030001 Taiyuan, Shanxi, China.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Niu
authors.affiliation: Department of Pediatrics, Peking University First Hospital, 100034 Beijing, China. Electronic address: wang66jm@163.com.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, 100034 Beijing, China. Electronic address: jiangyw@263.net.
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D018991:Myelin Proteolipid Protein / Q000235:genetics* / Q000378:metabolism; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human
keywords: Missense mutation; PLP1; PMD; Subcellular localization