A PLP splicing abnormality is associated with an unusual presentation of PMD.
Ann Neurol
; 52(4): 477-88, 2002 Oct.
Article
en En
| MEDLINE
| ID: mdl-12325077
ABSTRACT
We report that a deletion of 19 base pairs (bp) in intron 3 of the proteolipid protein (PLP/DM20) gene causes a neurological disease characterized by mild developmental delay, followed by progressive decline of acquired motor and cognitive milestones. The clinical features are associated with mild delay in myelination demonstrated by magnetic resonance imaging studies and with ongoing demyelination and axonal loss demonstrated by magnetic resonance spectroscopy. We demonstrate that the purine-rich 19bp element regulates PLP-specific splice site selection in transient transfections of chimeric constructs into cultured oligodendrocytes. Runs of 4 and 5 Gs centered in the 19bp element are critical for efficient PLP-specific splicing. The intronic element is sequence specific in oligodendrocytes and is not a repressor of PLP-specific splicing in nonglial cells. These data support the conclusion that deletion of the 19bp purine-rich region in PLP intron 3 causes a reduction in PLP message and protein, which affects myelin stability and axonal integrity.
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Banco de datos:
MEDLINE
Asunto principal:
Empalme del ARN
/
Eliminación de Gen
/
Proteína Proteolipídica de la Mielina
/
Enfermedad de Pelizaeus-Merzbacher
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Año:
2002
Tipo del documento:
Article