Familial hypophosphatemic rickets caused by a PHEX gene mutation accompanied by a NPR2 missense mutation

Background Familial hypophosphatemic rickets, which is usually acknowledged as X-linked hypophosphatemic rickets (XLH), is a rare hereditary disease. XLH caused by mutations in the PHEX gene often manifests as growth retardation, skeletal deformities, osteodynia and dental dysplasia. NPR2 mutations are reported to cause disproportionate short stature. Our study was designed to identify the gene mutations of three patients in one family. Case description A 40-year-old Chinese male visited the hospital for continuous osteodynia and presented with bilateral leg bowing, absent teeth and a progressive limp. The age of onset was approximately 2 years old. His 63-year-old mother and 42-year-old brother both shared identical symptoms with him. The laboratory tests were consistent with XLH, which showed decreased levels of blood phosphorus and 1,25-dihydroxyvitamin D3 as well as increased urinary phosphorus excretion. Mutation analysis revealed that the proband as well as his mother and his brother all had a PHEX mutation in exon 14 (c.1543C > T), and the proband also had a NPR2 mutation in exon 21 (c.3058C > T). Conclusions We report the familial hypophosphatemic rickets of three patients in a Chinese family caused by a PHEX gene mutation in exon 14 (c.1543C > T), which had never been reported in Chinese patients. We first report an XLH case together with a NPR2 mutation that had never been reported before.