Clinical and genetic analysis in a large Chinese cohort of patients with X-linked hypophosphatemia.

X-linked Hypophosphatemia (XLH) is caused by loss of function mutations in the PHEX gene. Given the recent availability of a new therapy for XLH, a retrospective analysis of the most recent 261 Chinese patients with XLH evaluated at Peking Union Medical College Hospital was conducted. Clinical, biochemical, radiographic studies, as well as genetic analyses, including Sanger sequencing for point mutations and Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large deletions/duplications were employed. Based on the structure of Neprilysin (NEP), a member of M13 family that includes PHEX, a three-dimensional (3D) model of PHEX was constructed, missense and nonsense mutations were positioned on the predicted structure to visualize relative positions of these two types of variants. Sex differences and genotype-phenotype correlations were also undertaken.