RESEARCH: HSP -- SPG2

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

studies in oligodendrocytes.

Hobson GM, Huang Z, Sperle K, Sistermans E, Rogan PK, Garbern JY, Kolodny E,

Naidu S, Cambi F.

Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Nemours

Children's Clinic, Wilmington, Delaware.

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.

SOURCE: Hum Mutat. 2005 Nov 14

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

6287154 & dopt=Abstract