Two novel PHEX mutations in Taiwanese patients with X-linked hypophosphatemic rickets.
BACKGROUND
X-linked hypophosphatemic rickets (XLH) is an X-linked dominant disease characterized by renal phosphate wasting, hypophosphatemia, aberrant vitamin D metabolism, and defective bone mineralization. The disease is caused by mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X-chromosome) located at Xp22.1. To date, a variety of PHEX mutations have been identified in these patients.


METHODS
PCR and direct sequencing was performed for all exons and intron-exon boundaries of the PHEX gene in two XLH families.


RESULTS
Two novel mutations, including a missense mutation (L206W) in exon 5 and a frameshift mutation (nucleotide 1826_1830delAAAAG, stop after codon 610) in exon 18 were discovered and the laboratory and radiographic findings for these patients analyzed.


CONCLUSIONS
We found that PHEX gene mutations were responsible for XLH in these Taiwanese patients. Additional studies are needed to enhance understanding of the role of PHEX in XLH pathogenesis.
Lo
Fu-Sung
FS
Department of Pediatrics, Division of Endocrinology, Chang Gung Children Hospital, Kweishan, Taoyuan, Taiwan. lofusu@adm.cgmh.org.tw
Kuo
Min-Tzu
MT
Wang
Chao-Jan
CJ
Chang
Chia-Hsieh
CH
Lee
Zhon-Liau
ZL
Van
Yang-Hau
YH
D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D007223:Infant; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008666:Metalloendopeptidases / Q000235:genetics*; D009154:Mutation; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; D010375:Pedigree; D011859:Radiography; D013624:Taiwan
D008562:Membrane Glycoproteins; D008666:Metalloendopeptidases; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human