Novel PHEX mutation associated with hypophosphatemic rickets.
BACKGROUND
X-linked hypophosphatemia (XLH) is the most prevalent heritable form of rickets. It is a dominantly inherited disorder, characterized by renal phosphate wasting, abnormal vitamin D and PTH metabolism, and defective bone mineralization. Inactivating mutations in the gene encoding PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) have been found to be associated with XLH.


METHODS
We report about a 54-year-old male patient who exhibited the typical features of XLH, and in whom mutational analysis using PCR and sequencing was performed. Additionally, extensive laboratory and radiological investigations were carried out.


RESULTS
A 1-bp deletion in exon 2 of the PHEX gene was detected (177delC), which, to the best of our knowledge, has not been reported yet. This deletion results in a premature stop codon (C59X), suggesting a truncation of the PHEX protein. Furthermore, elevated FGF23 and PTH levels as well as an increased axial bone mineral density score were measured.


CONCLUSIONS
We present a male patient with XLH, who harbors a novel mutation in the PHEX gene, which might be the cause for his disease. Our data support previous findings and therefore contribute to the decipherment of the pathogenetic pathways of XLH.
Roetzer
Katharina M
KM
Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 4th Medical Department, Hanusch Hospital, Vienna, Austria.
Varga
Franz
F
Zwettler
Elisabeth
E
Nawrot-Wawrzyniak
Kamilla
K
Haller
Joerg
J
Forster
Ernst
E
Klaushofer
Klaus
K
D001483:Base Sequence; D053098:Familial Hypophosphatemic Rickets / Q000175:diagnosis* / Q000235:genetics*; D000089703:Fibroblast Growth Factor-23; D040181:Genetic Diseases, X-Linked; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
C000717427:FGF23 protein, human; D000089703:Fibroblast Growth Factor-23; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human