Urinary tract effects of HPSE2 mutations

Helen M. Stuart, Neil A. Roberts, Emma N. Hilton, Edward A. McKenzie, Sarah B. Daly, Kristen D. Hadfield, Jeffery S. Rahal, Natalie J. Gardiner, Simon W. Tanley, Malcolm A. Lewis, Emily Sites, Brad Angle, Cláudia Alves, Teresa Lourenço, Márcia Rodrigues, Angelina Calado, Marta Amado, Nancy Guerreiro, Inês Serras, Christian BeetzRita Eva Varga, Mesrur Selcuk Silay, John M. Darlow, Mark G. Dobson, David E. Barton, Manuela Hunziker, Prem Puri, Sally A. Feather, Judith A. Goodship, Timothy H J Goodship, Heather J. Lambert, Heather J. Cordell, Anand Saggar, Maria Kinali, J. Beattie, M. Bradbuty, N. Coad, M. Coulthard, P. Cuckow, J. Dossetor, J. Dudley, D. Hughes, M. Fitzpatrick, N. Griffin, A. M. Gullett, G. Haycock, D. Hodes, P. Houtman, A. Hughes, S. Hulton, E. Hunter, J. Iqbal, C. Inward, J. Jackson, L. Jadresic, M. Jaswon, C. Jones, R. Jones, B. Judd, M. Kier, A. Kilby, M. Lewis, S. Malcolm, S. Marks, H. Maxwell, M. McGraw, D. Milford, N. Moghal, M. O'Connor, D. J. O'Donoghue, M. Ognanovic, N. Plant, R. Postlethwaite, L. Rees, C. Reid, E. Rfidah, S. Rigdon, R. Sandford, M. Savage, J. Scanlan, S. Sinha, S. Stephens, A. Stewart, J. Storr, S. Taheri, C. M. Taylor, J. Tizard, R. Trompeter, K. Tullus, I. Verber, W. Van't Hoff, S. Vernon, K. Verrier-Jones, A. Watson, N. Webb, D. Wilcox, Christian Lorenz, Kristina Moeller, Franz Schaefer, Aysun K. Bayazit, Stefanie Weber, William G. Newman, Adrian S. Woolf, N. Aksu, H. Alpay, A. Anarat, K. Arbeiter, G. L. Ardissino, A. Balat, E. Baskin, A. Bayazit, R. Büscher, N. Cakar, A. Caldas Afonso, S. Caliskan, C. Candan, N. Canpolat, O. Donmez, A. Doyon, D. Drozdz, J. Dusek, A. Duzova, S. Emre, H. Erdogan, M. Feldkötter, M. Fischbach, G. Galiano, D. Haffner, J. Harambat, A. Jankauskiene, N. Jeck, U. John, T. Jungraithmair, M. Kemper, A. Kiyak, D. Kracht, B. Kranz, G. Laube, M. Litwin, C. M. Matteucci, G. Montini, A. Melk, S. Mir, A. Niemirska, A. Peco-Antic, G. Ozcelik, E. Pelan, S. Picca, M. Pohl, U. Querfeld, B. Ranchin, R. Shroff, G. Simonetti, B. Sözeri, O. Soylemezoglu, Y. Tabel, S. Testa, A. Trivelli, E. Vidal, M. Wigger, E. Wühl, S. Wygoda, F. Yalcinkaya, E. Yilmaz, R. Zeller, A. M. Zurowska

Research output: Contribution to journalArticlepeer-review


Urofacial syndrome (UFS) is an autosomal recessive congenital disease featuring grimacing and incomplete bladder emptying. Mutations of HPSE2, encoding heparanase 2, a heparanase 1 inhibitor, occur in UFS, but knowledge about the HPSE2 mutation spectrum is limited. Here, seven UFS kindreds with HPSE2 mutations are presented, including one with deleted asparagine 254, suggesting a role for this amino acid, which is conserved in vertebrate orthologs. HPSE2 mutations were absent in 23 non-neurogenic neurogenic bladder probands and, of 439 families with nonsyndromic vesicoureteric reflux, only one carried a putative pathogenic HPSE2 variant. Homozygous Hpse2 mutant mouse bladders contained urine more often than did wild-type organs, phenocopying human UFS. Pelvic ganglia neural cell bodies contained heparanase 1, heparanase 2, and leucine-rich repeats and immunoglobulin-like domains-2 (LRIG2), which is mutated in certain UFS families. In conclusion, heparanase 2 is an autonomic neural protein implicated in bladder emptying, but HPSE2 variants are uncommon in urinary diseases resembling UFS.

Original languageEnglish
Pages (from-to)797-804
Number of pages8
JournalJournal of the American Society of Nephrology
Issue number4
Publication statusPublished - Apr 1 2015

ASJC Scopus subject areas

  • Nephrology


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