Publication: Urinary Tract Effects of HPSE2 Mutations
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Date
2015-04-01T00:00:00Z
Authors
Authors
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.
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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.
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Keywords
Genetics and development, Human genetics, Molecular genetics, Pediatric nephrology
Citation
Stuart H. M. , Roberts N. A. , Hilton E. N. , McKenzie E. A. , Daly S. B. , Hadfield K. D. , Rahal J. S. , Gardiner N. J. , Tanley S. W. , Lewis M. A. , et al., -Urinary Tract Effects of HPSE2 Mutations-, JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, cilt.26, ss.797-804, 2015