X-linked hypophosphatemic rickets (XLHR) is the most common form of inherited rickets caused by pathogenic variants of PHEX gene with an X-linked dominant inheritance pattern.
The most common heritable disorder of renal phosphate wasting, X-linked hypophosphataemia (XLH), was discovered to be caused by inactivating mutations in the phosphate regulating gene with homology to endopeptidases on the X-chromosome (PHEX) gene in 1995.
The role of FGF23 in the pathophysiology of XLH is here reviewed by describing what is known about phenotypes associated with various PHEX mutations, animal models of XLH, and non-nutritional diseases of hypophosphatemia, and by presenting molecular pathways that have been proposed to contribute to manifestations of XLH.
XLH is associated with a large number of private mutations; 37 different mutations in the PHEX gene were identified in this cohort, 14 of which have not been previously reported.
XLH is associated with a large number of private mutations; 37 different mutations in the PHEX gene were identified in this cohort, 14 of which have not been previously reported.
Using Raman spectroscopy, the carbonate (CO<sub>3</sub><sup>2-</sup>) to phosphate (PO<sub>4</sub><sup>3-</sup>) ion ratio was measured in HYP and wild-type mice and in primary and permanent teeth from XLH individuals and unaffected controls.
X-linked hypophosphatemia (XLH) is a skeletal disorder arising from mutations in the PHEX gene, transmitted in most cases as an X-linked dominant trait.
PHEX deficiency in XLH/Hyp dramatically alters the periodontal phenotype, with hypoplasia of tooth root cementum associated with a lack of periodontal ligament attachment and the presence of an immature apatitic mineral phase of all periodontal mineralized tissues.
Seven young patients with X-linked hypophosphatemia (XLH, having inactivating PHEX mutations) were discovered to accumulate osteopontin (OPN) at the sites of defective bone mineralization near osteocytes - the so-called hallmark periosteocytic (lacunar) "halos" of XLH.
X-linked hypophosphatemia (XLH) caused by mutations in the Phex gene is the most common human inherited phosphate wasting disorder characterized by enhanced synthesis of fibroblast growth factor 23 (FGF23) in bone, renal phosphate wasting, 1,25(OH)<sub>2</sub>D<sub>3</sub> (1,25D) deficiency, rickets and osteomalacia.
A compilation of XLH mutation hotspots based on the PHEX gene database and mutations found in the FGF23, DMP1, and ENPP1 genes are also made available in this review.