title: NPT4, a new microsomal phosphate transporter: mutation analysis in glycogen storage disease type Ic.
abstract: Deficiency of a microsomal phosphate transporter in the liver has been suggested in some patients affected by glycogen storage disease type Ic (GSD Ic). Several Na(+)/phosphate co-transporters have been characterized as members of the anion-cation symporter family. Recently, the cDNA sequence of two phosphate transporters, NPT3 and NPT4, expressed in liver, kidney and intestine, has been determined. We studied expression of human NPT4 in COS cells and observed an ER localization of the transporter by immunofluorescence microscopy. We speculated that this transporter could play a role in the regulation of the glucose-6-phosphatase (G6-Pase) complex. We revealed the genomic structure of NPT4 and analysed the gene as a candidate for GSD Ic. DNA was collected from five patients without mutations in G6-Pase or the G6-P transporter gene. DNA analysis of NPT4 revealed that one patient was heterozygous for a G>A transition at nucleotide 601 which would result in a G201R substitution. Our results do not confirm the hypothesis that this gene is mutated in GSD Ic patients. However, we cannot exclude that the mutation found reduces the phosphate transport efficiency, possibly modulating the G6-Pase complex.
authors.affiliation: Department of Clinical Genetics, Erasmus University Rotterdam, The Netherlands. danlis@tin.it
authors.forename: D
authors.initials: D
authors.lastname: Melis
authors.forename: A C
authors.initials: AC
authors.lastname: Havelaar
authors.forename: E
authors.initials: E
authors.lastname: Verbeek
authors.forename: G P A
authors.initials: GP
authors.lastname: Smit
authors.forename: A
authors.initials: A
authors.lastname: Benedetti
authors.forename: G M S
authors.initials: GM
authors.lastname: Mancini
authors.forename: F
authors.initials: F
authors.lastname: Verheijen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005455:Fluorescent Antibody Technique; D005822:Genetic Vectors; D005953:Glycogen Storage Disease Type I / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D027981:Symporters / Q000235:genetics*; D014162:Transfection
chemical_list: D018076:DNA, Complementary; C493550:SLC17A3 protein, human; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D027981:Symporters