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Urinary Tract Effects of HPSE2 Mutations
Stuart, H M; Roberts, N A; Hilton, E N; McKenzie, E A; Daly, S B; Hadfield, K D; Rahal, J S; Gardiner, N J; Tanley, S W; Lewis, M A; Sites, E; Angle, B; Alves, C; Lourenco, T; Rodrigues, M; Calado, A; Amado, M; Guerreiro, N; Serras, I; Beetz, C; Varga, R E; Silay, M S; Darlow, J M; Dobson, M G; Barton, D E; Hunziker, M; Puri, P; Feather, S A; Goodship, J A; Goodship, T H; Lambert, H J; Cordell, H J; Saggar, A; Kinali, M; Lorenz, C; Moeller, K; Schaefer, F; Bayazit, A K; Weber, S; Newman, W G; Woolf, A S
J Am Soc Nephrol. 2014;.
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Abstract
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.
Bibliographic metadata
- Stuart, H M
- Roberts, N A
- Hilton, E N
- McKenzie, E A
- Daly, S B
- Hadfield, K D
- Rahal, J S
- Gardiner, N J
- Tanley, S W
- Lewis, M A
- Sites, E
- Angle, B
- Alves, C
- Lourenco, T
- Rodrigues, M
- Calado, A
- Amado, M
- Guerreiro, N
- Serras, I
- Beetz, C
- Varga, R E
- Silay, M S
- Darlow, J M
- Dobson, M G
- Barton, D E
- Hunziker, M
- Puri, P
- Feather, S A
- Goodship, J A
- Goodship, T H
- Lambert, H J
- Cordell, H J
- Saggar, A
- Kinali, M
- Lorenz, C
- Moeller, K
- Schaefer, F
- Bayazit, A K
- Weber, S
- Newman, W G
- Woolf, A S
- Related website http://www.ncbi.nlm.nih.gov/pubmed/25145936
- Stuart, Helen M Roberts, Neil A Hilton, Emma N McKenzie, Edward A Daly, Sarah B Hadfield, Kristen D Rahal, Jeffery S Gardiner, Natalie J Tanley, Simon W Lewis, Malcolm A Sites, Emily Angle, Brad Alves, Claudia Lourenco, Teresa Rodrigues, Marcia Calado, Angelina Amado, Marta Guerreiro, Nancy Serras, Ines Beetz, Christian Varga, Rita-Eva Silay, Mesrur Selcuk Darlow, John M Dobson, Mark G Barton, David E Hunziker, Manuela Puri, Prem Feather, Sally A Goodship, Judith A Goodship, Timothy H J Lambert, Heather J Cordell, Heather J the UK VUR Study Group Saggar, Anand Kinali, Maria the 4C Study Group Lorenz, Christian Moeller, Kristina Schaefer, Franz Bayazit, Aysun K Weber, Stefanie Newman, William G Woolf, Adrian S J Am Soc Nephrol. 2014 Aug 21. pii: ASN.2013090961.