A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic Rickets
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 chromos...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2015-01-01
|
Series: | Case Reports in Genetics |
Online Access: | http://dx.doi.org/10.1155/2015/301264 |
id |
doaj-483a745caea74465a3159b8ebc275fd5 |
---|---|
record_format |
Article |
spelling |
doaj-483a745caea74465a3159b8ebc275fd52020-11-24T22:59:57ZengHindawi LimitedCase Reports in Genetics2090-65442090-65522015-01-01201510.1155/2015/301264301264A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic RicketsTetsuya Kawahara0Hiromi Watanabe1Risa Omae2Toshiyuki Yamamoto3Tetsuya Inazu4Division of Endocrinology and Metabolism, Department of Internal Medicine, Niigata Rosai Hospital, Niigata 9428502, JapanDepartment of Clinical Laboratory, Niigata National Hospital, Niigata 9458585, JapanDepartment of Pharmacy, College of Pharmaceutical Sciences, Ritsumeikan University, Shiga 5258577, JapanTokyo Women’s Medical University, Institute of Integrated Medical Sciences, Tokyo 1620054, JapanDepartment of Pharmacy, College of Pharmaceutical Sciences, Ritsumeikan University, Shiga 5258577, JapanX-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.http://dx.doi.org/10.1155/2015/301264 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tetsuya Kawahara Hiromi Watanabe Risa Omae Toshiyuki Yamamoto Tetsuya Inazu |
spellingShingle |
Tetsuya Kawahara Hiromi Watanabe Risa Omae Toshiyuki Yamamoto Tetsuya Inazu A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic Rickets Case Reports in Genetics |
author_facet |
Tetsuya Kawahara Hiromi Watanabe Risa Omae Toshiyuki Yamamoto Tetsuya Inazu |
author_sort |
Tetsuya Kawahara |
title |
A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic Rickets |
title_short |
A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic Rickets |
title_full |
A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic Rickets |
title_fullStr |
A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic Rickets |
title_full_unstemmed |
A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic Rickets |
title_sort |
novel phex mutation in japanese patients with x-linked hypophosphatemic rickets |
publisher |
Hindawi Limited |
series |
Case Reports in Genetics |
issn |
2090-6544 2090-6552 |
publishDate |
2015-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2015/301264 |
work_keys_str_mv |
AT tetsuyakawahara anovelphexmutationinjapanesepatientswithxlinkedhypophosphatemicrickets AT hiromiwatanabe anovelphexmutationinjapanesepatientswithxlinkedhypophosphatemicrickets AT risaomae anovelphexmutationinjapanesepatientswithxlinkedhypophosphatemicrickets AT toshiyukiyamamoto anovelphexmutationinjapanesepatientswithxlinkedhypophosphatemicrickets AT tetsuyainazu anovelphexmutationinjapanesepatientswithxlinkedhypophosphatemicrickets AT tetsuyakawahara novelphexmutationinjapanesepatientswithxlinkedhypophosphatemicrickets AT hiromiwatanabe novelphexmutationinjapanesepatientswithxlinkedhypophosphatemicrickets AT risaomae novelphexmutationinjapanesepatientswithxlinkedhypophosphatemicrickets AT toshiyukiyamamoto novelphexmutationinjapanesepatientswithxlinkedhypophosphatemicrickets AT tetsuyainazu novelphexmutationinjapanesepatientswithxlinkedhypophosphatemicrickets |
_version_ |
1725643126202171392 |