title: Proteolipid protein 1 gene mutation in nine patients with Pelizaeus-Merzbacher disease.
abstract: BACKGROUND
  Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive disorder with symptoms including nystagmus, impaired motor development, ataxia, and progressive spasticity. The proteolipid protein 1 (PLP1) gene is the only pathogenic gene of PMD. Duplication of the PLP1 gene is the most frequent gene defect, accounting for 50%-70% of PMD cases, whereas point mutations in the coding sequence or the splice sites account for 10%-25% of PMD cases. This study aimed to identify PLP1 mutations in nine unrelated Chinese patients (P1-9) with PMD, and 14 subjects from the family of patient 2 were also described.
  
  
  METHODS
  Genomic DNA was extracted from peripheral blood samples. Gene dosage was determined using the multiplex ligation-dependent probe amplification (MLPA). All 7 exons and exon-intron boundaries of the PLP1 gene were amplified and analyzed using direct DNA sequencing.
  
  
  RESULTS
  Of these nine patients, there were four transitional, four classical, and one connatal PMD according to their clinical and radiological presentations. PLP1 duplications were identified in patients 1-7 with PMD. Their mothers were PLP1 duplications carriers as well. Both duplication carriers and normal genotypes of PLP1 were identified in the family members of patient 2. A c.517C > T (p. P173S) hemizygous missense mutation in exon 4 was found in patient 8 with PMD, and his mother was shown to be a heterozygote of this mutation.
  
  
  CONCLUSIONS
  We identified seven genomic duplications and one missense mutation (p. P173S) of the PLP1 gene in eight Chinese patients with PMD. This is the report about PLP1 mutations in PMD patients from the mainland of China.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Jing-Min
authors.initials: JM
authors.lastname: Wang
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Wang
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Deng
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Yang
authors.forename: Jiong
authors.initials: J
authors.lastname: Qin
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Li
authors.forename: Xi-Ru
authors.initials: XR
authors.lastname: Wu
authors.forename: Yu-Wu
authors.initials: YW
authors.lastname: Jiang
mesh_terms: D002675:Child, Preschool; D005260:Female; D020440:Gene Duplication; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human