Urinary Tract Effects of HPSE2 Mutations

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 HPSE...

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Detalhes bibliográficos
Autor principal: Stuart, H (author)
Outros Autores: Roberts, N (author), Hilton, E (author), McKenzie, E (author), Daly, S (author), Hadfield, K (author), Rahal, J (author), Gardiner, N (author), Tanley, S (author), Lewis, M (author), Sites, E (author), Angle, B (author), Alves, C (author), Lourenço, T (author), Rodrigues, M (author), Calado, A (author), Amado, M (author), Guerreiro, N (author), Serras, I (author), Beetz, C (author), Varga, R (author), Silay, M (author), Darlow, J (author), Dobson, M (author), Barton, D (author), Hunziker, M (author), Puri, P (author), Feather, S (author), Goodship, J (author), Goodship, T (author), Lambert, H (author), Cordell, H (author), Saggar, A (author), Kinali, M (author), Lorenz, C (author), Moeller, K (author), Schaefer, F (author), Bayazit, A (author), Weber, S (author), Newman, W (author), Woolf, A (author)
Formato: article
Idioma:eng
Publicado em: 2016
Assuntos:
Animals
Facies
Female
Glucuronidase
Humans
Male
Mice
Mice, Inbred C57BL
Mutation
Urinary Tract
Urologic Diseases
HDE GEN
Texto completo:http://hdl.handle.net/10400.17/2500
País:Portugal
Oai:oai:repositorio.chlc.min-saude.pt:10400.17/2500
Descrição
Resumo: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.

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