Muscarinic Acetylcholine Receptor M3 Mutation Causes Urinary Bladder Disease and a Prune-Belly-like Syndrome

Am J Hum Genet. 2011 Nov 11;89(5):668-74. doi: 10.1016/j.ajhg.2011.10.007.


Urinary bladder malformations associated with bladder outlet obstruction are a frequent cause of progressive renal failure in children. We here describe a muscarinic acetylcholine receptor M3 (CHRM3) (1q41-q44) homozygous frameshift mutation in familial congenital bladder malformation associated with a prune-belly-like syndrome, defining an isolated gene defect underlying this sometimes devastating disease. CHRM3 encodes the M3 muscarinic acetylcholine receptor, which we show is present in developing renal epithelia and bladder muscle. These observations may imply that M3 has a role beyond its known contribution to detrusor contractions. This Mendelian disease caused by a muscarinic acetylcholine receptor mutation strikingly phenocopies Chrm3 null mutant mice.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Consanguinity
  • Female
  • Frameshift Mutation / genetics
  • Humans
  • INDEL Mutation / genetics
  • Immunohistochemistry
  • Male
  • Metabolism, Inborn Errors / genetics*
  • Mice
  • Mice, Knockout
  • Models, Molecular
  • Prune Belly Syndrome / genetics*
  • Prune Belly Syndrome / pathology
  • Receptor, Muscarinic M3* / deficiency
  • Receptor, Muscarinic M3* / genetics
  • Sequence Homology, Nucleic Acid
  • Sex Factors
  • Urinary Bladder Neck Obstruction / genetics
  • Urinary Bladder Neck Obstruction / pathology
  • Urinary Bladder* / embryology
  • Urinary Bladder* / pathology


  • Receptor, Muscarinic M3