Gordon RJ, Li D, Doyle D, et al. - Researchers conducted this retrospective and prospective analysis for identifying a genetic cause of apparent dominant transmission of Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH). Four affected and 3 unaffected members of a four-generation family were recruited in which the proband presented with apparent HHRH. They identify a kindred with autosomal dominant hypophosphatemic rickets in which digenic heterozygous mutations in SLC34A1 and SLC34A3 were found in the exome analysis. Individuals with both mutations were affected more severely than subjects with only one mutation. Such results illustrate the difficulties of assigning causality to plausible genetic variants in the next generation sequencing era.