Human Molecular Genetics, Vol 6, 539-549, Copyright © 1997 by Oxford University Press
PS Rowe, CL Oudet, F Francis, C Sinding, S Pannetier, MJ Econs, TM Strom, T Meitinger, M Garabedian, A David, MA Macher, E Questiaux, E Popowska, E Pronicka, AP Read, A Mokrzycki, FH Glorieux, MK Drezner, A Hanauer, H Lehrach, JN Goulding and JL O'Riordan
Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with
homologies to endopeptidases, on the X-chromosome), are responsible for
X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family
of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has
raised important questions regarding PEX function at the molecular level.
The aim of this study was to analyse 99 HYP families for PEX gene
mutations, and to correlate predicted changes in the protein structure with
Zn2+ metallopeptidase gene function. Primers flanking 22 characterised
exons were used to amplify DNA by PCR, and SSCP was then used to screen for
mutations. Deletions, insertions, nonsense mutations, stop codons and
splice mutations occurred in 83% of families screened for in all 22 exons,
and 51% of a separate set of families screened in 17 PEX gene exons.
Missense mutations in four regions of the gene were informative regarding
function, with one mutation in the Zn2+-binding site predicted to alter
substrate enzyme interaction and catalysis. Computer analysis of the
remaining mutations predicted changes in secondary structure,
N-glycosylation, protein phosphorylation and catalytic site molecular
structure. The wide range of mutations that align with regions required for
protease activity in NEP suggests that PEX also functions as a protease,
and may act by processing factor(s) involved in bone mineral metabolism.
ARTICLES
Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)
Department of Medicine, University College London, Middlesex Hospital, UK.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Saito, Y. Nishii, T. Yasuda, N. Ito, H. Suzuki, T. Igarashi, S. Fukumoto, and T. Fujita Familial hypophosphatemic rickets caused by a large deletion in PHEX gene Eur. J. Endocrinol., October 1, 2009; 161(4): 647 - 651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kim, K. H. Yang, J. S. Nam, J. R. Choi, J. Song, M. Chang, and K.-A Lee A Novel PHEX Mutation in a Korean Patient with Sporadic Hypophosphatemic Rickets Ann. Clin. Lab. Sci., January 1, 2009; 39(2): 182 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Martin, V. David, J. S. Laurence, P. M. Schwarz, E. M. Lafer, A.-M. Hedge, and P. S. N. Rowe Degradation of MEPE, DMP1, and Release of SIBLING ASARM-Peptides (Minhibins): ASARM-Peptide(s) Are Directly Responsible for Defective Mineralization in HYP Endocrinology, April 1, 2008; 149(4): 1757 - 1772. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Liu, P. S N Rowe, L. Vierthaler, J. Zhou, and L D. Quarles Phosphorylated acidic serine-aspartate-rich MEPE-associated motif peptide from matrix extracellular phosphoglycoprotein inhibits phosphate regulating gene with homologies to endopeptidases on the X-chromosome enzyme activity J. Endocrinol., January 1, 2007; 192(1): 261 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Syal, S. Schiavi, S. Chakravarty, V. Dwarakanath, R. Quigley, and M. Baum Fibroblast growth factor-23 increases mouse PGE2 production in vivo and in vitro Am J Physiol Renal Physiol, February 1, 2006; 290(2): F450 - F455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Khardori Editorial: Refeeding Syndrome and Hypophosphatemia J Intensive Care Med, May 1, 2005; 20(3): 174 - 175. [PDF]
|
|
|
|
|
|
M. Baum, O. W. Moe, J. Zhang, V. Dwarakanath, and R. Quigley Phosphatonin washout in Hyp mice proximal tubules: evidence for posttranscriptional regulation Am J Physiol Renal Physiol, February 1, 2005; 288(2): F363 - F370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Boccia, M. Petrillo, D. di Bernardo, A. Guffanti, F. Mignone, S. Confalonieri, L. Luzi, G. Pesole, G. Paolella, A. Ballabio, et al. DG-CST (Disease Gene Conserved Sequence Tags), a database of human-mouse conserved elements associated to disease genes Nucleic Acids Res., January 1, 2005; 33(suppl_1): D505 - D510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Bresler, J. Bruder, K. Mohnike, W. D Fraser, and P. S N Rowe Serum MEPE-ASARM-peptides are elevated in X-linked rickets (HYP): implications for phosphaturia and rickets J. Endocrinol., December 1, 2004; 183(3): R1 - R9. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. S.N. Rowe THE WRICKKENED PATHWAYS OF FGF23, MEPE AND PHEX Critical Reviews in Oral Biology & Medicine, September 1, 2004; 15(5): 264 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Baum, S. Loleh, N. Saini, M. Seikaly, V. Dwarakanath, and R. Quigley Correction of proximal tubule phosphate transport defect in Hyp mice in vivo and in vitro with indomethacin PNAS, September 16, 2003; 100(19): 11098 - 11103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-Y. Bai, D. Miao, D. Goltzman, and A. C. Karaplis The Autosomal Dominant Hypophosphatemic Rickets R176Q Mutation in Fibroblast Growth Factor 23 Resists Proteolytic Cleavage and Enhances in Vivo Biological Potency J. Biol. Chem., March 7, 2003; 278(11): 9843 - 9849. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Bai, D. Miao, D. Panda, S. Grady, M. D. McKee, D. Goltzman, and A. C. Karaplis Partial Rescue of the Hyp Phenotype by Osteoblast-Targeted PHEX (Phosphate-Regulating Gene with Homologies to Endopeptidases on the X Chromosome) Expression Mol. Endocrinol., December 1, 2002; 16(12): 2913 - 2925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Carpinelli, I. P. Wicks, N. A. Sims, K. O'Donnell, K. Hanzinikolas, R. Burt, S. J. Foote, M. Bahlo, W. S. Alexander, and D. J. Hilton An Ethyl-Nitrosourea-Induced Point Mutation in Phex Causes Exon Skipping, X-Linked Hypophosphatemia, and Rickets Am. J. Pathol., November 1, 2002; 161(5): 1925 - 1933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Jan De Beur and M. A. Levine Molecular Pathogenesis of Hypophosphatemic Rickets J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2467 - 2473. [Full Text] [PDF]
|
|
|
|
|
|
P. T. Christie, B. Harding, M. A. Nesbit, M. P. Whyte, and R. V. Thakker X-Linked Hypophosphatemia Attributable to Pseudoexons of the PHEX Gene J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3840 - 3844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. A. Holm, A. E. Nelson, B. G. Robinson, R. S. Mason, D. J. Marsh, C. T. Cowell, and T. O. Carpenter Mutational Analysis and Genotype-Phenotype Correlation of the PHEX Gene in X-Linked Hypophosphatemic Rickets J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3889 - 3899. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Sabbagh, G. Boileau, L. DesGroseillers, and H. S. Tenenhouse Disease-causing missense mutations in the PHEX gene interfere with membrane targeting of the recombinant protein Hum. Mol. Genet., July 1, 2001; 10(15): 1539 - 1546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P S N ROWE The molecular background to hypophosphataemic rickets Arch. Dis. Child., September 1, 2000; 83(3): 192 - 194. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lee, M. Lin, A. Mele, Y. Cao, J. Farmar, D. Russo, and C. Redman Proteolytic Processing of Big Endothelin-3 by the Kell Blood Group Protein Blood, August 15, 1999; 94(4): 1440 - 1450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ecarot and M. Desbarats 1,25-(OH)2D3 Down-Regulates Expression of Phex, a Marker of the Mature Osteoblast Endocrinology, March 1, 1999; 140(3): 1192 - 1199. [Abstract] [Full Text]
|
|
|
|
|
|
M. J. Econs, N. E. Friedman, P. S. N. Rowe, M. C. Speer, F. Francis, T. M. Strom, C. Oudet, J. A. Smith, J. T. Ninomiya, B. E. Lee, et al. A PHEX Gene Mutation Is Responsible for Adult-Onset Vitamin D-Resistant Hypophosphatemic Osteomalacia: Evidence That the Disorder Is Not a Distinct Entity from X-Linked Hypophosphatemic Rickets J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3459 - 3462. [Abstract] [Full Text]
|
|
|
|
|
|
P. H. Dixon, P. T. Christie, C. Wooding, D. Trump, M. Grieff, I. Holm, J. M. Gertner, J. Schmidtke, B. Shah, N. Shaw, et al. Mutational Analysis of PHEX Gene in X-Linked Hypophosphatemia J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3615 - 3623. [Abstract] [Full Text]
|
|
|
|
|
|
M. L. Lipman, D. Panda, H. P. J. Bennett, J. E. Henderson, E. Shane, Y. Shen, D. Goltzman, and A. C. Karaplis Cloning of Human PEX cDNA. EXPRESSION, SUBCELLULAR LOCALIZATION, AND ENDOPEPTIDASE ACTIVITY J. Biol. Chem., May 29, 1998; 273(22): 13729 - 13737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Russo, C. Redman, and S. Lee Association of XK and Kell Blood Group Proteins J. Biol. Chem., May 29, 1998; 273(22): 13950 - 13956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Econs and F. Francis Positional cloning of the PEX gene: new insights into the pathophysiology of X-linked hypophosphatemic rickets Am J Physiol Renal Physiol, October 1, 1997; 273(4): F489 - F498. [Abstract] [Full Text] [PDF]
|
|