Mutational survey of the PHEX gene in patients with X-linked hypophosphatemic rickets.
X-linked hypophosphatemic rickets (XLH) is a dominantly inherited disorder characterized by renal phosphate wasting, aberrant vitamin D metabolism, and abnormal bone mineralization. XLH is caused by inactivating mutations in PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). In this study, we sequenced the PHEX gene in subjects from 26 kindreds who were clinically diagnosed with XLH. Sequencing revealed 18 different mutations, of which thirteen have not been reported previously. In addition to deletions, splice site mutations, and missense and nonsense mutations, a rare point mutation in the 3'-untranslated region (3'-UTR) was identified as a novel cause of XLH. In summary, we identified a wide spectrum of mutations in the PHEX gene. Our data, in accord with those of others, indicate that there is no single predominant PHEX mutation responsible for XLH.
Ichikawa
Shoji
S
Department of Medicine, Indiana University School of Medicine, 541 North Clinical Drive, Indianapolis, IN 46202, USA.
Traxler
Elizabeth A
EA
Estwick
Selina A
SA
Curry
Leah R
LR
Johnson
Michelle L
ML
Sorenson
Andrea H
AH
Imel
Erik A
EA
Econs
Michael J
MJ
D020413:3' Untranslated Regions / Q000235:genetics; D004252:DNA Mutational Analysis; D053098:Familial Hypophosphatemic Rickets / Q000175:diagnosis / Q000235:genetics*; D040181:Genetic Diseases, X-Linked; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D009154:Mutation; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics*; D016133:Polymerase Chain Reaction
D020413:3' Untranslated Regions; D053402:PHEX Phosphate Regulating Neutral Endopeptidase