Targeted therapy for inherited GPI deficiency.
N Engl J Med
; 356(16): 1641-7, 2007 Apr 19.
Article
en En
| MEDLINE
| ID: mdl-17442906
ABSTRACT
Disrupted binding of the transcription factor Sp1 to the mutated promoter region of the mannosyl transferase-encoding gene PIGM causes inherited glycosylphosphatidylinositol (GPI) deficiency characterized by splanchnic vein thrombosis and epilepsy. We show that this results in histone hypoacetylation at the promoter of PIGM. The histone deacetylase inhibitor butyrate increases PIGM transcription and surface GPI expression in vitro as well as in vivo through enhanced histone acetylation in an Sp1-dependent manner. More important, the drug caused complete cessation of intractable seizures in a child with inherited GPI deficiency.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transcripción Genética
/
Butiratos
/
Factor de Transcripción Sp1
/
Glicosilfosfatidilinositoles
/
Inhibidores de Histona Desacetilasas
/
Manosiltransferasas
/
Errores Innatos del Metabolismo
Tipo de estudio:
Etiology_studies
Límite:
Adolescent
/
Female
/
Humans
Idioma:
En
Revista:
N Engl J Med
Año:
2007
Tipo del documento:
Article
País de afiliación:
Reino Unido