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

作者:Araya K; Fukumoto S*; Backenroth R; Takeuchi Y; Nakayama K; Ito N; Yoshii N; Yamazaki Y; Yamashita T; Silver J; Igarashi T; Fujita T
来源:Journal of Clinical Endocrinology & Metabolism, 2005, 90(10): 5523-5527.
DOI:10.1210/jc.2005-0301

摘要

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.
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.

  • 出版日期2005-10