Three novel PHEX gene mutations in four Chinese families with X-linked dominant hypophosphatemic rickets.
BACKGROUND
X-linked hypophosphatemia (XLH), the most common form of inherited rickets, is a dominant disorder that is characterized by renal phosphate wasting with hypophosphatemia, abnormal bone mineralization, short stature, and rachitic manifestations. The related gene with inactivating mutations associated with XLH has been identified as PHEX, which is a phosphate-regulating gene with homologies to endopeptidases on the X chromosome. In this study, a variety of PHEX mutations were identified in four Chinese families with XLH.


METHODS
We investigated four unrelated Chinese families who exhibited typical features of XLH by using PCR to analyze mutations that were then sequenced. The laboratory and radiological investigations were conducted simultaneously.


RESULTS
Three novel mutations were found in these four families: one frameshift mutation, c.2033dupT in exon 20, resulting in p.T679H; one nonsense mutation, c.1294A>T in exon 11, resulting in p.K432X; and one missense mutation, c.2192T>C in exon 22, resulting in p.F731S.


CONCLUSIONS
We found that the PHEX gene mutations were responsible for XLH in these Chinese families. Our findings are useful for understanding the genetic basis of Chinese patients with XLH.
Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, PR China.
Qing-lin
QL
Kang
Jia
J
Xu
Zeng
Z
Zhang
Jin-wei
JW
He
Lian-song
LS
Lu
Wen-zhen
WZ
Fu
Zhen-lin
ZL
Zhang
D000328:Adult; D044466:Asian People / Q000235:genetics; D002648:Child; D002681:China; D018389:Codon, Nonsense; D053098:Familial Hypophosphatemic Rickets / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D040181:Genetic Diseases, X-Linked; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics*; D010375:Pedigree; D055815:Young Adult
D018389:Codon, Nonsense; D053402:PHEX Phosphate Regulating Neutral Endopeptidase