Whole exome sequencing investigation of UTR variants that may dictate CYP24A1 intracellular activity

Hypomorphic mutations in the CYP24A1 protein coding region causing persistently elevated active vitamin D metabolites have been observed in some cases of idiopathic infantile hypercalcemia (IIH) and adult onset nephrolithiasis. It is unclear why some cases present with superficial CYP24A1 mediated hypercalcemia but do not exhibit CYP24A1 mutations. Here we used next generation sequencing to investigate CYP24A1 mutations in a patient cohort with superficial CYP24A1 mediated hypercalcemia. We report several single nucleotide variants located in the CYP24A1 UTR. Our results provide a framework that can be used to better understand the molecular basis of pathogenesis in hypercalcaemic patients lacking CYP24A1 protein coding region abnormalities.