Identification of two novel mutations in the PHEX gene in Chinese patients with hypophosphatemic rickets/osteomalacia.
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.
Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
Hua
H
Yue
Department of pediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
Jin-bo
JB
Yu
Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
Jin-wei
JW
He
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.
Zeng
Z
Zhang
Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
Wen-zhen
WZ
Fu
Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
Hao
H
Zhang
Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
Chun
C
Wang
Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
Wei-wei
WW
Hu
Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
Jie-mei
JM
Gu
Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
Yun-qiu
YQ
Hu
Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
Miao
M
Li
Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
Yu-juan
YJ
Liu
Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.
Zhen-Lin
ZL
Zhang
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D053098:Familial Hypophosphatemic Rickets / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010018:Osteomalacia / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics*; D010375:Pedigree; D011859:Radiography
D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human