Abstract | CONTEXT: OBJECTIVE: The objective of the study was to determine the relationship between GALNT3 and FGF23 in familial TC. DESIGN, SETTING, AND PATIENTS: We assessed the major biochemical defects and potential genes involved in patients with TC. INTERVENTION: RESULTS: We report a patient homozygous for a GALNT3 exon 1 deletion, which is predicted to truncate the encoded protein. This patient had high serum FGF23 concentrations when assessed with a C-terminal FGF23 ELISA but low-normal FGF23 levels when tested with an ELISA for intact FGF23 concentrations. Matrix extracellular phosphoglycoprotein has been identified as a possible regulator of phosphate homeostasis. Serum matrix extracellular phosphoglycoprotein levels, however, were normal in the family with GALNT3-TC and a kindred with TC carrying the FGF23 S71G mutation. The tumoral masses of the patient with GALNT3-TC completely resolved after combination therapy. CONCLUSIONS: Our findings demonstrate that GALNT3 inactivation in patients with TC leads to inadequate production of biologically active FGF23 as the most likely cause of the hyperphosphatemic phenotype. Furthermore, combination therapy may be effective for reducing the tumoral burden associated with familial TC.
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Authors | Holly J Garringer, Corinne Fisher, Tobias E Larsson, Siobhan I Davis, Daniel L Koller, Michael J Cullen, Mohamad S Draman, Niamh Conlon, Alka Jain, Neal S Fedarko, Bhaskar Dasgupta, Kenneth E White |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 91
Issue 10
Pg. 4037-42
(Oct 2006)
ISSN: 0021-972X [Print] United States |
PMID | 16868048
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Extracellular Matrix Proteins
- FGF23 protein, human
- Glycoproteins
- MEPE protein, human
- Neoplasm Proteins
- Phosphates
- Phosphoproteins
- Fibroblast Growth Factors
- Fibroblast Growth Factor-23
- N-Acetylgalactosaminyltransferases
- Calcitriol
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Topics |
- Amino Acid Sequence
- Base Sequence
- Calcinosis
(blood, genetics, therapy)
- Calcitriol
(blood)
- Extracellular Matrix Proteins
(blood)
- Fibroblast Growth Factor-23
- Fibroblast Growth Factors
(blood, genetics)
- Glycoproteins
(blood)
- Humans
- Molecular Sequence Data
- Mutation
- N-Acetylgalactosaminyltransferases
(genetics, physiology)
- Neoplasm Proteins
(genetics, physiology)
- Phosphates
(blood)
- Phosphoproteins
(blood)
- Polypeptide N-acetylgalactosaminyltransferase
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