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J Clin Endocrinol Metab. 2005 Oct;90(10):5523-7. Epub 2005 Jul 19.

A novel mutation in fibroblast growth factor 23 gene as a cause of tumoral calcinosis.

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  • 1Department of Pediatrics, University of Tokyo Hospital, 3-28-6, Bunkyo-ku, Tokyo 113-8655, Japan.

Abstract

CONTEXT:

Tumoral calcinosis is a disease characterized by ectopic calcification and hyperphosphatemia due to enhanced renal tubular phosphate reabsorption. Fibroblast growth factor (FGF)23 was identified as a responsible factor in hypophosphatemic diseases caused by renal phosphate leak.

OBJECTIVE:

The objective of the study was to analyze the involvement of FGF23 in the development of tumoral calcinosis.

DESIGN:

Serum FGF23 level was evaluated in a patient with tumoral calcinosis by two kinds of ELISA: full-length assay that detects only full-length FGF23 with phosphate-lowering activity and C-terminal assay that measures full-length as well as C-terminal fragment of FGF23. FGF23 gene was analyzed by direct sequencing of PCR products, and mutant FGF23 was analyzed by Western blotting after expression in mammalian cells.

PATIENTS:

A family of tumoral calcinosis patients were studied.

RESULTS:

Serum FGF23 was extremely high when measured by C-terminal assay. In contrast, it was low normal by full-length assay. Analysis of FGF23 gene detected a serine to phenylalanine mutation in codon 129. No wild-type allele of this codon was found in the patient. The brother of the proband showed the same base change. When this mutant FGF23 was expressed in vitro, full-length and N-terminal fragments were barely detectable by Western blotting, whereas C-terminal fragment with the same molecular weight as that from wild-type FGF23 could be detected.

CONCLUSION:

The production and serum level of C-terminal fragment of FGF23 are increased in this patient with tumoral calcinosis. Together with the recent similar report of FGF23 mutation, impaired action of full-length FGF23 seems to result in tumoral calcinosis.

PMID:
16030159
[PubMed - indexed for MEDLINE]
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