caa a22 4500 469044713 CHVBK 20180323132821.0 cr unu---uuuuu 170328e19920701xx s 000 0 eng 10.1007/BF01799618 doi (NATIONALLICENCE)springer-10.1007/BF01799618 X-linked hypophosphataemia: A homologous phenotype in humans and mice with unusual organ-specific gene dosage [Elektronische Daten] [C. Scriver, H. Tenenhouse] Summary: XLH (X-linked hypophosphataemia, gene symbolHYP, McKusick 307800, 307810) and its murine counterparts (Hyp andGy) map to a conserved segment on the X-chromosome (Xp 22.31-p.21.3, human; distal X, mouse). Gene dosage has received relatively little attention in the long history of research on this disease, which began over 50 years ago. Bone and teeth are sites of the principal disease manifestations in XLH (rickets, osteomalacia, interglobular dentin). Newer measures of quantitative XLH phenotypes reveal gene dose effects in bone and teeth with heterozygous values distributed between those in mutant hemizygotes and normal homozygotes. On the other hand, serum phosphate concentrations (which are low in the mutant phenotype and thereby contribute to bone and tooth phenotypes) do not show gene dosage. InHyp mice serum values in mutant hemizygotes, mutant homozygotes and heterozygotes are similar. Phosphate homeostasis reflects its renal conservation. Renal absorption of phosphate on a high-affinity, Na+ ion-gradient coupled system in renal brush border membrane is impaired and gene dosage is absent at this level; the mutant phenotype is fully dominant. Synthesis and degradation of 1,25(OH)2D are also abnormal in XLH (andHyp), but gene dosage in these parameters has not yet been measured. An (unidentified) inhibitory trans-acting product of the X-linked locus, affecting phosphate transport and vitamin D metabolism, acting perhaps through cytosolic protein kinase C, could explain the renal phenotype. But why would it have a normal gene dose effect in bone and teeth? Since the locus may have duplicated (to formHyp andGy), and shows evidence of variable expression in different organs (inner ear, bone/teeth, kidney), it may have been recruited during evolution to multiple functions. SSIEM and Kluwer Academic Publishers, 1992 Scriver C. The MRC Group in Medical Genetics, Departments of Biology and Pediatrics, and Centre for Human Genetics, McGill University, Montreal, Quebec, Canada aut Tenenhouse H. The MRC Group in Medical Genetics, Departments of Biology and Pediatrics, and Centre for Human Genetics, McGill University, Montreal, Quebec, Canada aut Journal of Inherited Metabolic Disease Kluwer Academic Publishers 15/4(1992-07-01), 610-624 0141-8955 15:4<610 1992 15 10545 https://doi.org/10.1007/BF01799618 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01799618 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Scriver C. The MRC Group in Medical Genetics, Departments of Biology and Pediatrics, and Centre for Human Genetics, McGill University, Montreal, Quebec, Canada aut NATIONALLICENCE 700 1- Tenenhouse H. The MRC Group in Medical Genetics, Departments of Biology and Pediatrics, and Centre for Human Genetics, McGill University, Montreal, Quebec, Canada aut NATIONALLICENCE 773 0- Journal of Inherited Metabolic Disease Kluwer Academic Publishers 15/4(1992-07-01), 610-624 0141-8955 15:4<610 1992 15 10545 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer