Mutational analysis and genotype-phenotype correlation of the PHEX gene inX-linked hypophosphatemic rickets

PHEX is the gene defective in X-linked hypophosphatemic rickets. In this st udy, analysis of PHEX revealed mutations in 22 hypophosphatemic rickets pat ients, including 16 of 28 patients in whom all 22 PHEX exons were studied. In 13 patients, in whom no PHEX mutation had been previously detected in 17 exons, the remaining 5 PHEX exons were analyzed and mutations found in 6 p atients. Twenty different mutations were identified, including 16 mutations predicted to truncate PHEX and 4 missense mutations. Phenotype analysis was performed on 31 hypophosphatemic rickets patients wi th PHEX mutations, including the 22 patients identified in this study, 9 pa tients previously identified, and affected family members. No correlation w as found between the severity of disease and the type or location of the mu tation. However, among patients with a family history of hypophosphatemic r ickets, there was a trend toward more severe skeletal disease in patients w ith truncating mutations. Family members in more recent generations had a m ilder phenotype. Postpubertal males had a more severe dental phenotype. In conclusion, although identifying mutations in PHEX may have limited prognos tic value, genetic testing may be useful for the early identification and t reatment of affected individuals. Furthermore, this study suggests that oth er genes and environmental factors affect the severity of hypophosphatemic rickets.