X-linked hypophosphatemia. A phenotype in search of a cause.
XLH is an important disease, it is the subject of several classic articles in the medical sciences (Scriver et al., 1991), and it has been an important stimulus to study renal hypophosphatemias and how they are involved in rickets and osteomalacia (Scriver, 1974; Scriver and Tenenhouse, 1991). Renal transport is the major determinant of phosphate homeostasis in mammals and it is unlikely that this important biochemical parameter would have been left by evolution to a single renal transport system. Together physiologists and geneticists found that the mammalian kidney has several gene products dedicated to phosphate transport. That has implications for biochemists in search of a membrane protein to clone and explain XLH, for example. Let us suppose the transporter affected in XLH is cloned. Will it be the product of the XLH (or Hyp or Gy) locus? One will not know until the transporter gene is mapped. There is no question of the X-chromosome locus product being protein kinase C for example, since it maps to autosomes. But where does one start in the search for the X-chromosome locus? With the elusive putative diffusible factor or with the transporter, or perhaps with an enzyme in vitamin D hormone metabolism? Which goes to say that it is necessary to know the phenotype to arrive at the right locus. Or is it? Sufficient physical mapping of region Xp22.31-p21.3 will eventually lead to positional cloning of the Hyp gene. What will it be?(ABSTRACT TRUNCATED AT 250 WORDS)
Tenenhouse
H S
HS
McGill University-Montreal Children's Hospital Research Institute, DeBelle Laboratory for Biochemical Genetics, Department of Pediatrics and Biology, Quebec, Canada.
Scriver
C R
CR
D000818:Animals; D008040:Genetic Linkage; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D014960:X Chromosome