Mutations in HPSE2 Cause Urofacial Syndrome

Sarah Daly, Jill E. Urquhart, Emma Hilton, Edward A. McKenzie, Richard Kammerer, Malcolm Lewis, Bronwyn Kerr, Helen Stuart, Dian Donnai, David A. Long, Berk Burgu, Ozgu Aydogdu, Murat Derbent, Sixto Garcia-Minaur, Willie Reardon, Blanca Gener, Stavit Shalev, Rupert Smith, Adrian Woolf, Graeme C. BlackWilliam G. Newman

    Research output: Contribution to journalArticlepeer-review


    Urinary voiding dysfunction in childhood, manifesting as incontinence, dysuria, and urinary frequency, is a common condition. Urofacial syndrome (UFS) is a rare autosomal recessive disease characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. UFS individuals often have reflux of infected urine from the bladder to the upper renal tract, with a risk of kidney damage and renal failure. Whole-genome SNP mapping in one affected individual defined an autozygous region of 16 Mb on chromosome 10q23-q24, within which a 10 kb deletion encompassing exons 8 and 9 of HPSE2 was identified. Homozygous exonic deletions, nonsense mutations, and frameshift mutations in five further unrelated families confirmed HPSE2 as the causative gene for UFS. Mutations were not identified in four additional UFS patients, indicating genetic heterogeneity. We show that HPSE2 is expressed in the fetal and adult central nervous system, where it might be implicated in controlling facial expression and urinary voiding, and also in bladder smooth muscle, consistent with a role in renal tract morphology and function. Our findings have broader implications for understanding the genetic basis of lower renal tract malformations and voiding dysfunction. © 2010 The American Society of Human Genetics.
    Original languageEnglish
    Pages (from-to)963-969
    Number of pages6
    JournalAmerican Journal of Human Genetics
    Issue number6
    Publication statusPublished - 11 Jul 2010


    • Brain/metabolism
    • Child
    • Child, Preschool
    • Chromosome Mapping
    • Chromosomes, Human, Pair 10
    • *Facies
    • Female
    • Genes, Recessive
    • Glucuronidase/chemistry/*genetics/metabolism
    • Humans
    • Male
    • Models, Molecular
    • Muscles/metabolism
    • Mutation
    • Pedigree
    • Syndrome
    • Urinary Bladder/metabolism
    • Urologic Diseases/*genetics

    Research Beacons, Institutes and Platforms

    • Manchester Institute of Biotechnology


    Dive into the research topics of 'Mutations in HPSE2 Cause Urofacial Syndrome'. Together they form a unique fingerprint.

    Cite this