The role of the PHEX gene (PEX) in families with X-linked hypophosphataemic rickets.
For over a hundred years, the bane of rickets (a disease of bone), has been prominent in those countries that have participated in, and seeded, the industrial revolution. Industrialisation had major effects of the demography of populations, and many people moved to dark, heavily industrialised cities to find work. It soon became apparent that rickets could be cured by supplementing the diet with cod liver oil and exposure to sunlight. This in turn led to the discovery that photoactivation of 7-dehydrocholesterol was required to produce vitamin D, an indispensable regulator of bone mineral metabolism. Although inadequate exposure to light and poor dietary intake are the main causes of rickets and osteomalacia, recent research has confirmed the role of familial, and tumour forms of the disease. This review will describe the recent advances in our knowledge of the molecular defects in X-linked hypophosphataemic rickets (HYP), and oncogenic hypophosphataemic osteomalacia (OHO). Although HYP and OHO have different primary defects, both diseases have similarities that suggest a linked or overlapping pathophysiology. Also, without doubt, the recent cloning of the gene defective in HYP (the PHEX gene), has given researchers a new reagent to explore the molecular regulation of bone and its links to kidney endocrine function. The fact that the PHEX gene codes for a Zn metallopeptidase raises new and intriguing questions, and adds new momentum to the research on diseases of bone mineral metabolism.
University of London, Royal Free Hospital School of Medicine, Department of Biochemistry and Molecular Biology, Hampstead, UK. peter.rowe@ucl.ac.uk
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D000818:Animals; D005192:Family Health; D005796:Genes / Q000235:genetics*; D006801:Humans; D017674:Hypophosphatemia / Q000235:genetics; D007015:Hypophosphatemia, Familial / Q000235:genetics*; D010018:Osteomalacia / Q000235:genetics; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; D011506:Proteins / Q000235:genetics / Q000502:physiology*
D011506:Proteins; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human