title: Splice-site contribution in alternative splicing of PLP1 and DM20: molecular studies in oligodendrocytes.
abstract: 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.
authors.affiliation: Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Nemours Children's Clinic, Wilmington, Delaware, USA. ghobson@nemours.org
authors.forename: Grace M
authors.initials: GM
authors.lastname: Hobson
authors.forename: Zhong
authors.initials: Z
authors.lastname: Huang
authors.forename: Karen
authors.initials: K
authors.lastname: Sperle
authors.forename: Erik
authors.initials: E
authors.lastname: Sistermans
authors.forename: Peter K
authors.initials: PK
authors.lastname: Rogan
authors.forename: James Y
authors.initials: JY
authors.lastname: Garbern
authors.forename: Edwin
authors.initials: E
authors.lastname: Kolodny
authors.forename: Sakkubai
authors.initials: S
authors.lastname: Naidu
authors.forename: Franca
authors.initials: F
authors.lastname: Cambi
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D005091:Exons / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007257:Information Theory; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D009836:Oligodendroglia / Q000378:metabolism*; D010641:Phenotype; D022821:RNA Splice Sites / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000166:cytology
chemical_list: D008565:Membrane Proteins; D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human; D022821:RNA Splice Sites; D012333:RNA, Messenger