Targeted therapy for inherited GPI deficiency

António M. Almeida; Yoshiko Murakami; Alastair Baker; Yusuke Maeda; Irene A.G. Roberts; Taroh Kinoshita; D. Mark Layton; Anastasios Karadimitris

doi:10.1056/NEJMoa063369

Targeted therapy for inherited GPI deficiency

António M. Almeida, Yoshiko Murakami, Alastair Baker, Yusuke Maeda, Irene A.G. Roberts, Taroh Kinoshita, D. Mark Layton, Anastasios Karadimitris^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

82 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1641-1647
Number of pages	7
Journal	New England Journal of Medicine
Volume	356
Issue number	16
DOIs	https://doi.org/10.1056/NEJMoa063369
Publication status	Published - 19 Apr 2007
Externally published	Yes

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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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AU - Almeida, António M.

AU - Murakami, Yoshiko

AU - Baker, Alastair

AU - Maeda, Yusuke

AU - Roberts, Irene A.G.

AU - Kinoshita, Taroh

AU - Layton, D. Mark

AU - Karadimitris, Anastasios

PY - 2007/4/19

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N2 - 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.

AB - 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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VL - 356

SP - 1641

EP - 1647

JO - New England Journal of Medicine

JF - New England Journal of Medicine

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Targeted therapy for inherited GPI deficiency

Abstract

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