Identification of two novel mutations in the PHEX gene in Chinese patients with hypophosphatemic rickets/osteomalacia

Hua Yue; Jin-bo Yu; Jin-wei He; Zeng Zhang; Wen-zhen Fu; Hao Zhang; Chun Wang; Wei-wei Hu; Jie-mei Gu; Yun-qiu Hu; Miao Li; Yu-juan Liu; Zhen-Lin Zhang

doi:10.1371/journal.pone.0097830

Identification of two novel mutations in the PHEX gene in Chinese patients with hypophosphatemic rickets/osteomalacia

PLoS One. 2014 May 16;9(5):e97830. doi: 10.1371/journal.pone.0097830. eCollection 2014.

Authors

Hua Yue¹, Jin-bo Yu², Jin-wei He¹, Zeng Zhang³, Wen-zhen Fu¹, Hao Zhang¹, Chun Wang¹, Wei-wei Hu¹, Jie-mei Gu¹, Yun-qiu Hu¹, Miao Li¹, Yu-juan Liu¹, Zhen-Lin Zhang¹

Affiliations

¹ Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
² Department of pediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
³ Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China; Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China.

Abstract

Objective: X-linked dominant hypophosphatemia (XLH) is the most prevalent form of inherited rickets/osteomalacia in humans. The aim of this study was to identify PHEX gene mutations and describe the clinical features observed in 6 unrelated Chinese families and 3 sporadic patients with hypophosphatemic rickets/osteomalacia.

Methods: For this study, 45 individuals from 9 unrelated families of Chinese Han ethnicity (including 16 patients and 29 normal phenotype subjects), and 250 healthy donors were recruited. All 22 exons and exon-intron boundaries of the PHEX gene were amplified by polymerase chain reaction (PCR) and directly sequenced.

Results: The PHEX mutations were detected in 6 familial and 3 sporadic hypophosphatemic rickets/osteomalacia. Altogether, 2 novel mutations were detected: 1 missense mutation c.1183G>C in exon 11, resulting in p.Gly395Arg and 1 missense mutation c.1751A>C in exon 17, resulting in p.His584Pro. No mutations were found in the 250 healthy controls.

Conclusions: Our study increases knowledge of the PHEX gene mutation types and clinical phenotypes found in Chinese patients with XLH, which is important for understanding the genetic basis of XLH. The molecular diagnosis of a PHEX genetic mutation is of great importance for confirming the clinical diagnosis of XLH, conducting genetic counseling, and facilitating prenatal intervention, especially in the case of sporadic patients.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Amino Acid Sequence
Case-Control Studies
Child
Child, Preschool
Familial Hypophosphatemic Rickets / complications
Familial Hypophosphatemic Rickets / diagnostic imaging
Familial Hypophosphatemic Rickets / genetics*
Female
Humans
Male
Middle Aged
Molecular Sequence Data
Mutation, Missense*
Osteomalacia / complications
Osteomalacia / diagnostic imaging
Osteomalacia / genetics*
PHEX Phosphate Regulating Neutral Endopeptidase / genetics*
Pedigree
Radiography

Substances

PHEX Phosphate Regulating Neutral Endopeptidase
PHEX protein, human

Grants and funding

The study was supported by grants from the National Natural ScienceFoundation of China (No. 81000360, 81170803, 81070692, and 81370978), Shanghai Rising-Star Program (No. 11QA1404900), and Academic Leaders in Health Sciences in Shanghai (No XBR2011014). The founder (Prof. Zhen-lin Zhang( with the National Natural Science Foundation of China (81170803 and 81070692) and Academic Leaders in Health Sciences in Shanghai (No XBR2011014) played a role in conceiving, designing, revising the study and data collection as well. The founder (Dr. Hua Yue) with the National Natural Science Foundation of China (No. 81000360) and Shanghai Rising-Star Program (No. 11QA1404900) was responsible for data analysis, writing, and preparation of the manuscript. The founder with the National Natural Science Foundation of China (No. 81370978) had a role in data collection.