Nature Genetics
11, 130 - 136 (1995)
doi:10.1038/ng1095-130
A gene (PEX) with homologies to endopeptidases is mutated in patients with X−linked hypophosphatemic ricketsF. Francis1, 4, S. Hennig1, 4, B. Korn2, 4, R. Reinhardt1, 4, P. de Jong3, 4, A. Poustka3, 4, H. Lehrach1, 4, P.S.N Rowe5, 9, J.N. Goulding5, 9, T. Summerfield5, 9, R. Mountford6, 9, A.P. Read6, 9, E. Popowska7, 9, E. Pronicka7, 9, K.E. Davies8, 9, J.L.H. O'Riordan5, 9, M.J. Econs10, 11, T. Nesbitt10, 11, M.K. Drezner10, 11, C. Oudet12, 13, S. Pannetier12, 13, A. Hanauer12, 13, T.M. Strom14, 16, A. Meindl14, 16, B. Lorenz14, 16, B. Cagnoli15, 16, K.L. Mohnike15, 16, J. Murken14, 16
& T. Meitinger14, 16
1Max−Planck Institut für Molekulare Genetik, 14195 Berlin, Germany
2Molekulare Genomanalyse, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, Germany
3Roswell Park Cancer Institute, Buffalo, NY 14263, USA
4The HYP Consortium, Group 1
5University College London, Dept. of Med., Middlesex Hospital, London W1N 8AA, UK
6Dept. of Med. Genetics, Manchester University, Manchester M13 OJH, UK
7Centrum Zdrowia Dziecka, Dept. of Metabolic Diseases, Warsaw, 04-736 Poland
8Molecular Genetics Group, John Radcliffe Hospital, Oxford OX3 9DU, UK
9The HYP Consortium, Group 2
10Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
11The HYP Consortium, Group 3
12IGBMC, Pare d'lnnovation, 67404 Illkirch, France
13The HYP Consortium, Group 4
14Abteilung für Pädiatrische Genetik, Kinderpoliklinik der Ludwig-Maximilian Universität, Goethestr. 29, 80336 München, Germany
15Zentrum für Kinderheilkunde, Otto-von-Guericke Universität, Wiener Str., 39112 Magdeburg, Germany
16The HYP Consortium, Group 5 Correspondence should be addressed to H.L. or T.M. X−linked hypophosphatemic rickets (HYP) is a dominant disorder characterised by impaired phosphate uptake in the kidney, which is likely to be caused by abnormal regulation of sodium phosphate cotransport in the proximal tubules. By positional cloning, we have isolated a candidate gene from the HYP region in Xp22.1. This gene exhibits homology to a family of endopeptidase genes, members of which are involved in the degradation or activation of a variety of peptide hormones. This gene (which we have called PEX) is composed of multiple exons which span at least five cosmids. Intragenic non−overlapping deletions from four different families and three mutations (two splice sites and one frameshift) have been detected in HYP patients, which suggest that the PEX gene is involved in the HYP disorder.
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