@article{503fe1e8df4a41a9b8d7c5528c0f6c1c,
title = "Urinary Tract Effects of HPSE2 Mutations",
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.",
keywords = "genetics and development, human genetics, molecular genetics, pediatric nephrology",
author = "Stuart, {H M} and Roberts, {N A} and Hilton, {E N} and Edward Mckenzie and Daly, {S B} and Hadfield, {K D} and Rahal, {J S} and Gardiner, {N J} and Tanley, {S W} and Lewis, {M A} and E Sites and B Angle and C Alves and T Lourenco and M Rodrigues and A Calado and M Amado and N Guerreiro and I Serras and C Beetz and Varga, {R E} and Silay, {M S} and Darlow, {J M} and Dobson, {M G} and Barton, {D E} and M Hunziker and P Puri and Feather, {S A} and Goodship, {J A} and Goodship, {T H} and Lambert, {H J} and Cordell, {H J} and {UK VUR Study Group} and A Saggar and M Kinali and C Lorenz and K Moeller and F Schaefer and Bayazit, {A K} and S Weber and Newman, {W G} and Woolf, {Adrian S}",
note = "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.",
year = "2015",
month = apr,
doi = "10.1681/ASN.2013090961",
language = "English",
volume = "26",
pages = "797--804",
journal = "J Am Soc Nephrol",
issn = "1533-3450",
publisher = "American Society of Nephrology",
number = "4",
}