Mutational analysis of PHEX, FGF23 and DMP1 in a cohort of patients with hypophosphatemic rickets

Abstract

X-linked hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets and autosomal recessive hypophosphatemic rickets make up a group of renal phosphate wasting disorders with common clinical and biochemical characteristics. These three types of rickets are related to mutations in PHEX, FGF23 and dentin matrix protein 1 (DMP1), respectively. The objective of the study was to evaluate the frequency of mutations that occur in these three genes associated with hypophosphatemic rickets. In this study, we sequenced these genes in 76 members of 46 kindreds from a large hypophosphatemic rickets cohort. Forty-two individuals from 27 kindreds were found to have mutations in PHEX; 16 of which were novel. One subject had an FGF23 mutation. No individuals were found to have mutations in DMP1 consistent with the presence of recessive hypophosphatemic rickets. Our data highlight the wide spectrum of genetic variation that can be seen in PHEX, FGF23 and DMP1 when screening a large cohort with hypophosphatemic rickets.