LRIG2 mutations cause urofacial syndrome

Am J Hum Genet. 2013 Feb 7;92(2):259-64. doi: 10.1016/j.ajhg.2012.12.002. Epub 2013 Jan 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Facies
  • Family
  • Female
  • Humans
  • Immunohistochemistry
  • Infant
  • Male
  • Membrane Glycoproteins / genetics*
  • Molecular Sequence Data
  • Mutation / genetics*
  • Pedigree
  • Urinary Bladder / pathology
  • Urinary Bladder, Neurogenic / genetics
  • Urologic Diseases / genetics*
  • Urologic Diseases / physiopathology


  • LRIG2 protein, human
  • Membrane Glycoproteins

Supplementary concepts

  • Urofacial syndrome

Associated data

  • GENBANK/JX891452