Summary Background 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 DMP1, respectively. Objective The objective of the study was to evaluate the frequency of mutations that occur in these three genes associated with hypophosphatemic rickets. Patients and Methods In this study, we sequenced these genes in 76 members of 46 kindreds from a large hypophosphatemic rickets cohort. Results 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. Conclusions 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.

BACKGROUND-Meningomyelocele (MM) is a common human birth defect. MM is a disorder of neural development caused by contributions from genes and environmental factors that result in the neural tube defect and lead to a spectrum of physical and neurocognitive phenotypes.

BACKGROUND-Neural tube defects (NTDs) occur in as many as 0.5-2 per 1000 live births in the United 'States. One of the most common and severe neural tube defects is meningomyelocele (MM) resulting from failed closure of the caudal end of the neural tube. MM has been induced by retinoic acid teratogenicity in rodent models. We hypothesized that genetic variants influencing retinoic acid (RA) induction via retinoic acid receptors (RARs) may be associated with risk for MM.