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Case Reports in Genetics
Volume 2015, Article ID 301264, 5 pages
Case Report

A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic Rickets

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Niigata Rosai Hospital, Niigata 9428502, Japan
2Department of Clinical Laboratory, Niigata National Hospital, Niigata 9458585, Japan
3Department of Pharmacy, College of Pharmaceutical Sciences, Ritsumeikan University, Shiga 5258577, Japan
4Tokyo Women’s Medical University, Institute of Integrated Medical Sciences, Tokyo 1620054, Japan
5Department of Clinical Research, Saigata National Hospital, Niigata 9493193, Japan

Received 18 January 2015; Revised 28 February 2015; Accepted 5 March 2015

Academic Editor: Mohnish Suri

Copyright © 2015 Tetsuya Kawahara et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


X-linked hypophosphatemic rickets (XLH) is a dominant inherited disorder characterized by renal phosphate wasting, aberrant vitamin D metabolism, and abnormal bone mineralization. Inactivating mutations in the gene encoding phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) have been found to be associated with XLH. Here, we report a 16-year-old female patient affected by hypophosphatemic rickets. We evaluated her serum fibroblast growth factor 23 (FGF23) levels and conducted sequence analysis of the disease-associated genes of FGF23-related hypophosphatemic rickets: PHEX, FGF23, dentin matrix protein 1, and ectonucleotide pyrophosphatase/phosphodiesterase 1. She was diagnosed with XLH based on her clinical features and family history. Additionally, we observed elevated FGF23 levels and a novel PHEX exon 9 mutation (c.947G>T; p.Gly316Val) inherited from her father. Although bioinformatics showed that the mutation was neutral, Gly316 is perfectly conserved among humans, mice, and rats, and there were no mutations in other FGF23-related rickets genes, suggesting that in silico analysis is limited in determining mutation pathogenicity. In summary, we present a female patient and her father with XLH harboring a novel PHEX mutation that appears to be causative of disease. Measurement of FGF23 for hypophosphatemic patients is therefore useful for the diagnosis of FGF23-dependent hypophosphatemia.