Genetic Mapping in the Xp11.2 Region of a New Form of X-Linked Hypophosphatemic Rickets

Abstract

Human X-linked dominant hypophosphatémie rickets (HPDR I) is characterized by hypophosphatemia, hyperphosphaturia, abnormal vitamin D metabolism, and rickets/osteomalacia. Two closely linked hypophosphatémie genes, hypophosphatemia (Hyp) and Gyro (Gy), are known on the mouse X chromosome. The Hyp phenotype is the equivalent of the human X-linked hypophosphatemia, while the human equivalent of the Gyro mouse has not been unambiguously identified. We observed an Italian four-generation pedigree with a new form of X-linked recessive hypophosphatémie rickets (XLRH). We demonstrated that HPDR I and XLRH are two different X-linked genes and that XLRH maps in the Xpl 1.2 region at 0% recombination fraction from the DXS1039 locus. We discuss this new finding in relation to the identification of the human equivalent of the Gyro mouse and to the recent mapping in Xpl 1.22 of another X-linked recessive renal disorder named Dent disease.