Hyperphosphatasia mental retardation syndrome (HPMR), an autosomal recessive disease characterized by mental retardation and elevated serum alkaline phosphatase (ALP) levels, is caused by mutations in the coding region of the phosphatidylinositol glycan anchor biosynthesis, class V (PIGV) gene, the product of which is a mannosyltransferase essential for glycosylphosphatidylinositol (GPI) biosynthesis. (nih.gov)
Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. (nih.gov)
Glycosylphosphatidylinositol biosynthesis defects (GPIBDs) cause a group of phenotypically overlapping recessive syndromes with intellectual disability, for which pathogenic mutations have been described in 16 genes of the corresponding molecular pathway. (biomedcentral.com)
Inherited deficiencies of glycosylphosphatidylinositol (GPI) biosynthesis are a heterogeneous group of recessive Mendelian disorders that all share a common feature: the function of GPI-linked proteins is compromised due to a defect in GPI anchor synthesis or modification. (biomedcentral.com)
The differentiation between early and late GPI anchor synthesis considers the molecular consequence of the glycosylphosphatidylinositol biosynthesis defect (GPIBD), which was suggested after an important finding from Murakami et al. (biomedcentral.com)
Deficiency4
In contrast, a previously reported PIGM deficiency, in which there is a defect in the transfer of the first mannose, does not result in hyperphosphatasia. (nih.gov)
3. Cerebral and portal vein thrombosis, macrocephaly and atypical absence seizures in Glycosylphosphatidyl inositol deficiency due to a PIGM promoter mutation. (nih.gov)
It results from a point mutation of PIGM, which reduces transcription of PIGM and blocks mannosylation of glycosylphosphatidylinositol (GPI), leading to partial but severe deficiency of GPI. (cdc.gov)
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. (ox.ac.uk)
Promoter1
We show that this results in histone hypoacetylation at the promoter of PIGM. (ox.ac.uk)
Transcription1
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. (ox.ac.uk)