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Previous Volume 356:1641-1647 April 19, 2007 Number 16 Next

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SUMMARY

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.

Source Information

From the Department of Haematology, Imperial College London, Hammersmith Hospital (A.M.A., I.A.G.R., D.M.L., A.K.), and the Paediatric Liver Centre, King's College Hospital (A.B.) — both in London; and the Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Osaka (Y. Murakami, Y. Maeda, T.K.), and the Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama (T.K.) — both in Japan.

Drs. Almeida and Murakami contributed equally to this article.

Address reprint requests to Dr. Karadimitris at the Department of Haematology, Imperial College London, Hammersmith Hospital, Du Cane Rd., London W12 0NN, United Kingdom, or at a.karadimitris{at}imperial.ac.uk.

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