LRIG2 mutations cause urofacial syndrome

  • Am J Hum Genet. 2013 Feb 7;92(2):259-64. doi: 10.1016/j.ajhg.2012.12.002.
Helen M Stuart  1 ,  Neil A Roberts ,  Berk Burgu ,  Sarah B Daly ,  Jill E Urquhart ,  Sanjeev Bhaskar ,  Jonathan E Dickerson ,  Murat Mermerkaya ,  Mesrur Selcuk Silay ,  Malcolm A Lewis ,  M Beatriz Orive Olondriz ,  Blanca Gener ,  Christian Beetz ,  Rita E Varga ,  Omer Gülpınar ,  Evren Süer ,  Tarkan Soygür ,  Zeynep B Ozçakar ,  Fatoş Yalçınkaya ,  Aslı Kavaz ,  Burcu Bulum ,  Adnan Gücük ,  Wyatt W Yue ,  Firat Erdogan ,  Andrew Berry ,  Neil A Hanley ,  Edward A McKenzie ,  Emma N Hilton ,  Adrian S Woolf ,  William G Newman
Affiliations
  • 1. Centre for Genetic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester and St. Mary's Hospital, Manchester Academic Health Science Centre, Manchester, UK.
PMID: 23313374 DOI: 10.1016/j.ajhg.2012.12.002
Abstract

Urofacial syndrome (UFS) (or Ochoa syndrome) is an autosomal-recessive disease characterized by congenital urinary bladder dysfunction, associated with a significant risk of kidney failure, and an abnormal facial expression upon smiling, laughing, and crying. We report that a subset of UFS-affected individuals have biallelic mutations in LRIG2, encoding leucine-rich repeats and immunoglobulin-like domains 2, a protein implicated in neural cell signaling and tumorigenesis. Importantly, we have demonstrated that rare variants in LRIG2 might be relevant to nonsyndromic bladder disease. We have previously shown that UFS is also caused by mutations in HPSE2, encoding heparanase-2. LRIG2 and heparanase-2 were immunodetected in nerve fascicles growing between muscle bundles within the human fetal bladder, directly implicating both molecules in neural development in the lower urinary tract.