title: A novel clinical syndrome revealing a deficiency of the muscarinic M3 receptor.
abstract: OBJECTIVE
  No clinical disorders have been caused by dysfunction of any of the 5 subtypes (M1-M5) of muscarinic receptors. We present a patient with a novel clinical syndrome that we suggest results from a deficiency of the muscarinic M3 receptor.
  
  
  METHODS
  We conducted a comprehensive workup of autonomic function. The patient's disorder was compared to the phenotypic features of male M3 knockout mice. M3 protein quantity was assessed by Western blot and radioligand binding in peripheral blood lymphocytes. Tests for autoantibodies and genetic abnormalities were performed.
  
  
  RESULTS
  The disease pattern was characterized by disturbances in micturition, pupil constriction, body weight, and sudomotor function, with normal accommodation, gastrointestinal motility, salivation, and lacrimation, similar to features of male M3 knockout mice. M3 protein quantity was reduced. Genetic tests were unrevealing, but unspecific antinuclear antibodies were present.
  
  
  CONCLUSIONS
  The presented clinical syndrome suggests a deficiency of the muscarinic M3 receptor. These results and future evaluation of patients with autonomic deficits may provide insights into the site and functional role of the muscarinic M3 receptor in humans.
authors.affiliation: Department of Cognitive Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany joern.pomper@uni-tuebingen.de
authors.forename: J K
authors.initials: JK
authors.lastname: Pomper
authors.forename: H
authors.initials: H
authors.lastname: Wilhelm
authors.forename: S K
authors.initials: SK
authors.lastname: Tayebati
authors.forename: F
authors.initials: F
authors.lastname: Asmus
authors.forename: R
authors.initials: R
authors.lastname: Schüle
authors.forename: K-D
authors.initials: KD
authors.lastname: Sievert
authors.forename: C-A
authors.initials: CA
authors.lastname: Haensch
authors.forename: A
authors.initials: A
authors.lastname: Melms
authors.forename: T
authors.initials: T
authors.lastname: Haarmeier
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D043587:Receptor, Muscarinic M3 / Q000172:deficiency* / Q000235:genetics*; D013577:Syndrome
chemical_list: D043587:Receptor, Muscarinic M3