title: A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic Rickets.
abstract: 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.
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine, Niigata Rosai Hospital, Niigata 9428502, Japan.
authors: Tetsuya
authors: T
authors: Kawahara
authors: Department of Clinical Laboratory, Niigata National Hospital, Niigata 9458585, Japan.
authors: Hiromi
authors: H
authors: Watanabe
authors: Department of Pharmacy, College of Pharmaceutical Sciences, Ritsumeikan University, Shiga 5258577, Japan.
authors: Risa
authors: R
authors: Omae
authors: Tokyo Women's Medical University, Institute of Integrated Medical Sciences, Tokyo 1620054, Japan.
authors: Toshiyuki
authors: T
authors: Yamamoto
authors: Department of Pharmacy, College of Pharmaceutical Sciences, Ritsumeikan University, Shiga 5258577, Japan ; Department of Clinical Research, Saigata National Hospital, Niigata 9493193, Japan.
authors: Tetsuya
authors: T
authors: Inazu