Abstract
X-linked dominant hypophosphatemia (XLH, OMIM307800), the most prevalent form of inherited rickets in humans, is a dominant disorder of phosphate homeostasis characterized by growth retardation, rachitic and osteomalacic bone disease, hypophosphatemia, and renal phosphate wasting. The gene responsible for XLH was identified by positional cloning and designated PHEX (formerly PEX) to depict a phosphate-regulating gene homologous with endopeptidases on the X chromosome. Recently, extensive mutation analysis of the PHEX gene has revealed a wide variety of gene defects in XLH. The ethnic distribution of the mutations is very widespread but only a few mutations in Chinese have been reported. To analyze the molecular basis in three unrelated Chinese families with XLH, we determined the nucleotide sequence of the PHEX gene and fibroblast growth factor 23 (FGF23) gene of affected members. The serum FGF23 concentrations of these patients with XLH were also measured. Three different novel mutations were observed in these three families: one deletion mutation c.264delG causing p.W88 X; one missense mutation c.1673C>G causing p.P558A; one nonsense mutation c.1809G>A causing p.W603 X. Serum concentration of FGF23 in XLH patients of these three families was significantly higher than normal. The results suggest that PHEX gene mutations were responsible for XLH in these patients and these mutations may contribute to a higher serum FGF23 level.
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Abbreviations
- ADHR:
-
Autosomal dominant hypophosphatemic rickets
- FGF23:
-
Fibroblast growth factor 23
- HHRH:
-
Hereditary hypophosphatemic rickets with hypercalciuria
- HR:
-
Hypophosphatemic rickets
- PHEX:
-
Phosphate-regulating gene with homologies to endopeptidases on X chromosome
- TIO:
-
Tumor-induced osteomalacia
- XLH:
-
X-linked dominant hypophosphatemic rickets
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Acknowledgments
The authors thank Dr. Huiyuan Luo (Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College) and Dr. David Huanzhu Ke (Department of Metabolic Disorders, Bone and Mineral Metabolism, Amgen, Inc.) who provided helpful discussion. They are also indebted to the support provided by the National Natural Science Foundation of China (NSFC) under grant No. 30370781 and Doctoral Fund of Ministry of Education of China under grant No. 20040023055.
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Xia, W., Meng, X., Jiang, Y. et al. Three Novel Mutations of the PHEX Gene in Three Chinese Families with X-linked Dominant Hypophosphatemic Rickets. Calcif Tissue Int 81, 415–420 (2007). https://doi.org/10.1007/s00223-007-9067-4
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DOI: https://doi.org/10.1007/s00223-007-9067-4