imagem top



CHULC LOGOlogo HDElogo anuario


Helen M. Stuart, Neil  A.  Roberts,  Emma  N.  Hilton, Edward  A.  McKenzie,  Sarah  B.  Daly, Kristen D. Hadfield, Jeffery S. Rahal, Natalie J. Gardiner, Simon W. Tanley, Malcolm A. Lewis, Emily Sites, Brad Angle, Cláudia Alves1, Teresa Lourenço2, Márcia Rodrigues2, Angelina Calado3, Marta Amado3, Nancy Guerreiro3, Inês Serras, Christian Beetz, Rita-Eva Varga, Mesrur Selcuk Silay, John M. Darlow, Mark G. Dobson, David E. Barton, Manuela Hunziker, Prem Puri, Sally A. Feather, Judith A. Goodship, Timothy H.J. Goodship, Heather J. Lambert, Heather J. Cordell, the UK VUR Study Group, Anand Saggar, Maria Kinali, the 4C Study Group, Christian Lorenz, Kristina Moeller, Franz Schaefer, Aysun K. Bayazit, Stefanie Weber, William G. Newman, and Adrian S. Woolf

1 - Genética e Diagnóstico Pré-Natal (GDPN)
2 - Especialidade de Genética Médica, Área Departamental de Pediatria Médica, Hospital de Dona Estefânia, Centro Hospitalar de Lisboa Central, EPE
3 - Serviço de Pediatria, Hospital de Portimão, Centro Hospitalar do Algarve, EPE

- JASN April 2015 26: 797-804. doi: 10.1681/ASN.2013090961. Epub 2014 Aug 21. (publicação sob a forma integral)

Introduction: 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.
Methods and results: 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.
Conclusion: In conclusion, heparanase 2 is an autonomic neural protein implicated in bladder emptying, but HPSE2 variants are uncommon in urinary diseases resembling UFS.

Palavras Chave: Urofacial syndrome, bladder emptying, gene HPSE2