TY - JOUR
T1 - Splice-site contribution in alternative splicing of PLP1 and DM20
T2 - Molecular studies in oligodendrocytes
AU - Hobson, Grace M.
AU - Huang, Zhong
AU - Sperle, Karen
AU - Sistermans, Erik
AU - Rogan, Peter K.
AU - Garbern, James Y.
AU - Kolodny, Edwin
AU - Naidu, Sakkubai
AU - Cambi, Franca
PY - 2006/1/1
Y1 - 2006/1/1
N2 - 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.
AB - 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.
KW - Alternative splicing
KW - Genotype-phenotype
KW - Information theory
KW - PLP1
KW - Pelizaeus-Merzbacher disease
KW - Proteolipid protein 1 gene
UR - http://www.scopus.com/inward/record.url?scp=29944434372&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/humu.20276
DO - https://doi.org/10.1002/humu.20276
M3 - Article
C2 - 16287154
SN - 1059-7794
VL - 27
SP - 69
EP - 77
JO - Human mutation
JF - Human mutation
IS - 1
ER -