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Urinary Tract Effects of HPSE2 Mutations

Lookup NU author(s): Professor Judith Goodship, Professor Tim Goodship, Dr Heather Lambert, Professor Heather Cordell


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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.

Publication metadata

Author(s): Stuart HM, Roberts NA, Hilton EN, McKenzie EA, Daly SB, Hadfield KD, Rahal JS, Gardiner NJ, Tanley SW, Lewis MA, Sites E, Angle B, Alves C, Lourenco T, Rodrigues M, Calado A, Amado M, Guerreiro N, Serras I, Beetz C, Varga RE, Silay MS, Darlow JM, Dobson MG, Barton DE, Hunziker M, Puri P, Feather SA, Goodship JA, Goodship THJ, Lambert HJ, Cordell HJ, Saggar A, Kinali M, Lorenz C, Moeller K, Schaefer F, Bayazit AK, Weber S, Newman WG, Woolf AS, UK VUR Study Grp, 4C Study Grp

Publication type: Article

Publication status: Published

Journal: Journal of the American Society of Nephrology

Year: 2015

Volume: 26

Issue: 4

Pages: 797-804

Print publication date: 01/04/2015

Online publication date: 21/08/2014

Acceptance date: 03/07/2014

ISSN (print): 1046-6673

ISSN (electronic): 1533-3450

Publisher: American Society of Nephrology


DOI: 10.1681/ASN.2013090961


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Funder referenceFunder name
Children's Medical & Research Foundation
European Renal Association-European Dialysis and Transplant Association (ERA-EDTA)
KfH Foundation for Preventive Medicine, Kidneys for Life, Kidney Research UK
01EO0802German Federal Ministry of Education and Research
066647Wellcome Trust
G0600040Medical Research Council
MR/L002744/1Medical Research Council