Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23

  title={Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23},
  author={Kenneth E White and Wayne E. Evans and Jeffery L.H. O'Riordan and Marcy C. Speer and Michael J. Econs and Bettina Lorenz-Depiereux and Monika Grabowski and Thomas Meitinger and Tim Matthias Strom},
  journal={Nature Genetics},
Proper serum phosphate concentrations are maintained by a complex and poorly understood process. Identification of genes responsible for inherited disorders involving disturbances in phosphate homeostasis may provide insight into the pathways that regulate phosphate balance. Several hereditary disorders of isolated phosphate wasting have been described, including X-linked hypophosphataemic rickets (XLH), hypophosphataemic bone disease (HBD), hereditary hypophosphataemic rickets with… 
Molecular Genetics of Inherited Hypophosphataemias
Intact plasma levels of the phosphatonin FGF23 are elevated in patients with ARHR, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH)(2)D levels found in this disease.
Hereditary hypophosphatemias: New genes in the bone–kidney axis (Review Article)
DMP1 and NaPi‐IIc add two new members to the bone–kidney axis proposed since it was discovered that the first phosphatonin, FGF23, was of osteoblastic/osteocyte origin.
Inherited hypophosphatemic disorders in children and the evolving mechanisms of phosphate regulation
The current understanding of hormonal and molecular mechanisms that govern phosphorous homeostasis is presented, and a protein with abundant expression in bone, fibroblast growth factor 23 (FGF23), has proven to be a circulating hormone that inhibits tubular reabsorption of phosphate in the kidney.
An autosomal dominant hypophosphatemic rickets phenotype in a Tunisian family caused by a new FGF23 missense mutation
A Tunisian family in which one parent and three children show clinical and biological features of ADHR is reported, confirming the importance of this site in FGF23 function and its essential role in ADHR physiopathology.
Novel PHEX Mutation Associated with Hypophosphatemic Rickets
A male patient with XLH is presented, who harbors a novel mutation in the PHEX gene, which might be the cause for his disease, and his data support previous findings and therefore contribute to the decipherment of the pathogenetic pathways of XLH.
Familial hypophosphatemic rickets caused by a large deletion in PHEX gene.
Careful genetic analysis is mandatory for correct differential diagnosis of hypophosphatemic rickets with high FGF23 levels and single nucleotide polymorphism analysis indicated that the mother has three kinds of PHEX alleles suggesting a somatic mosaic.
A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic Rickets
A 16-year-old female patient and her father are presented with XLH harboring a novel PHEX mutation that appears to be causative of disease, and measurement of FGF23 for hypophosphatemic patients is useful for the diagnosis of F GF23-dependent hypoph phosphatemia.
Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3.
Identification of the gene mutated in a further form of hypophosphatemia adds to the understanding of phosphate homeostasis and may help to elucidate the interaction of the proteins involved in this pathway.
Genetic basis of hereditary hypophosphataemic rickets and phenotype presentation in children and adults.
The clinical and biochemical characteristics presented in this review can help in the diagnosis of different types of HR and, therefore, direct genetic analysis to look for the specific gene mutation.
The expanding family of hypophosphatemic syndromes
  • T. Carpenter
  • Medicine, Biology
    Journal of Bone and Mineral Metabolism
  • 2011
Investigation of X-linked hypophosphatemia (XLH) has led to the identification of a novel phosphate-regulating homeostatic system and the FGF23 system serves as a novel mechanism by which the mineralizing skeleton can communicate phosphate supply to the kidney and thereby mediate excretion or conservation of this important skeletal component.


Autosomal dominant hypophosphatemic rickets/osteomalacia: clinical characterization of a novel renal phosphate-wasting disorder.
Renal phosphate-wasting disorders are the most common form of hereditary rickets and osteomalacia in western countries. Although autosomal dominant transmission of renal phosphate wasting has been
Autosomal dominant hypophosphatemic rickets is linked to chromosome 12p13.
These data are the first to establish a chromosomal location for the ADHR locus and to provide a framework map to further localize the gene and provide further insight into phosphate homeostasis.
Hereditary hypophosphatemic rickets with hypercalciuria.
It is proposed that the pivotal defect in this syndrome is a renal phosphate leak resulting in hypophosphatemia with an appropriate elevation of 1,25-dihydroxyvitamin D levels, which causes increased calcium absorption, parathyroid suppression, and hypercalciuria.
A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia
A systematic screening of FGFR3 to detect mutations in patients with hypochondroplasia is reported, with a singleFGFR3 mutation found in 8 out of 14 unrelated patients with HypochondroPLasia.
Hypophosphatemic nonrachitic bone disease: an entity distinct from X-linked hypophosphatemia in the renal defect, bone involvement, and inheritance.
It is proposed that some process regulates the distribution of phosphorus between serum and bone, and that this process is affected in different ways in HBD and XLH.
A gene (PEX) with homologies to endopeptidases is mutated in patients with X–linked hypophosphatemic rickets
Intragenic non–overlapping deletions from four different families and three mutations have been detected in HYP patients, which suggest that the PEX gene is involved in the HYP disorder.
Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome
Direct sequencing has revealed specific mutations in the B exon of FGFR2 in all nine sporadic and familial cases, including replacement of a cysteine in an immunoglobulin-like domain in five patients.
Tumor-induced osteomalacia--unveiling a new hormone.
Phosphate plays a critical part in the regulation of cell metabolism, and phosphate homeostasis is closely regulated in normal humans. Indeed, like serum calcium, serum phosphate is maintained within
Brief report: inhibition of renal phosphate transport by a tumor product in a patient with oncogenic osteomalacia.
This work investigated the ability of medium in which sclerosing hemangioma cells from a patient with oncogenic osteomalacia were cultured to alter sodium-dependent phosphate transport in opossum-kidney epithelial cells and found that the medium inhibited phosphate transport, without increasing.