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Splice‐site contribution in alternative splicing of PLP1 and DM20 : molecular studies in oligodendrocytes
Author(s) -
Hobson Grace M.,
Huang Zhong,
Sperle Karen,
Sistermans Erik,
Rogan Peter K.,
Garbern James Y.,
Kolodny Edwin,
Naidu Sakkubai,
Cambi Franca
Publication year - 2006
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20276
Subject(s) - biology , rna splicing , proteolipid protein 1 , genetics , alternative splicing , gene , splice , exon , rna , myelin , neuroscience , myelin basic protein , central nervous system
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. Hum Mutat 27(1), 69–77, 2006. © 2005 Wiley‐Liss, Inc.