Splice-site contribution in alternative splicing of PLP1 and DM20: Molecular studies in oligodendrocytes

Grace M. Hobson, Zhong Huang, Karen Sperle, Erik Sistermans, Peter K. Rogan, James Y. Garbern, Edwin Kolodny, Sakkubai Naidu, Franca Cambi

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Mutations in the proteolipid protein 1 (PLP1) gene cause the X-linked dysmyelinating diseases Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia 2 (SPG2). We examined the severity of the following mutations that were suspected of affecting levels of PLP1 and DM20 RNA, the alternatively spliced products of PLP1: c.453G>A, c.453G>T, c.453G>C, c.453+2T>C, c.453+4A>G, c.347C>A, and c.453+28_+ 46del (the old nomenclature did not include the methionine codon: G450A, G450T, G450C, IVS3+2T>C, IVS3+4A>G, C344A, and IVS3+28_+46del). These mutations were evaluated by information theory-based analysis and compared with mRNA expression of the alternatively spliced products. The results are discussed relative to the clinical severity of disease. We conclude that the observed PLP1 and DM20 splicing patterns correlated well with predictions of information theory-based analysis, and that the relative strength of the PLP1 and DM20 donor splice sites plays an important role in PLP1 alternative splicing.

Original languageEnglish (US)
Pages (from-to)69-77
Number of pages9
JournalHuman mutation
Issue number1
StatePublished - Jan 2006


  • Alternative splicing
  • Genotype-phenotype
  • Information theory
  • PLP1
  • Pelizaeus-Merzbacher disease
  • Proteolipid protein 1 gene

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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