Three novel PHEX gene mutations in Japanese patients with X-linked hypophosphatemic rickets

X-linked hypophosphatemic rickets (XLH) is an X-linked dominant disorder ch aracterized by renal phosphate wasting, abnormal vitamin D metabolism, and defects of bone mineralization. The phosphate-regulating gene on the X-chro mosome (PHEX) that is defective in XLH has been cloned, and its location id entified at Xp22.1. It has been recognized to be homologous to certain endo peptidases. So far, a variety of PHEX mutations have been identified mainly in European and North American patients with XLH. To analyze the molecular basis of four unrelated Japanese families with XLH, we determined the nucl eotide sequence of the PHEX gene of affected members. We detected a new non sense mutation (R198X) in exon 5, a new 3 nucleotides insertion mutation in exon 12 and a new missense mutation (L160R) in exon 5 as well as a previou sly reported nonsense mutation in exon 8 (R291X). These results suggest tha t: 1) PHEX gene mutations are responsible for XLH in Japanese patients, and 2) PHEX gene mutations are heterogeneous in the Japanese population simila rly to other ethnic populations.