Author(s):
Stuart, H ; Roberts, N ; Hilton, E ; McKenzie, E ; Daly, S ; Hadfield, K ; Rahal, J ; Gardiner, N ; Tanley, S ; Lewis, M ; Sites, E ; Angle, B ; Alves, C ; Lourenço, T ; Rodrigues, M ; Calado, A ; Amado, M ; Guerreiro, N ; Serras, I ; Beetz, C ; Varga, R ; Silay, M ; Darlow, J ; Dobson, M ; Barton, D ; Hunziker, M ; Puri, P ; Feather, S ; Goodship, J ; Goodship, T ; Lambert, H ; Cordell, H ; Saggar, A ; Kinali, M ; Lorenz, C ; Moeller, K ; Schaefer, F ; Bayazit, A ; Weber, S ; Newman, W ; Woolf, A
Date: 2015
Persistent ID: http://hdl.handle.net/10400.17/2500
Origin: Repositório do Centro Hospitalar de Lisboa Central, EPE
Subject(s): Animals; Facies; Female; Glucuronidase; Humans; Male; Mice; Mice, Inbred C57BL; Mutation; Urinary Tract; Urologic Diseases; HDE GEN
Description
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.
