OBJECTIVES: 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.
OBJECTIVES: 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: Stefanie Weber; Holger Thiele; Sevgi Mir; Mohammad Reza Toliat; Betül Sozeri; Heiko Reutter; Markus Draaken; Michael Ludwig; Janine Altmüller; Peter Frommolt; Helen M Stuart; Parisa Ranjzad; Neil A Hanley; Rachel Jennings; William G Newman; Duncan T Wilcox; Uwe Thiel; Karl Peter Schlingmann; Rolf Beetz; Peter F Hoyer; Martin Konrad; Franz Schaefer; Peter Nürnberg; Adrian S Woolf Journal: Am J Hum Genet Date: 2011-11-11 Impact factor: 11.025
Authors: Glenda M Beaman; Gabriella Galatà; Keng W Teik; Jill E Urquhart; Ali Aishah; James O'Sullivan; Sanjeev S Bhaskar; Katherine A Wood; Huw B Thomas; Raymond T O'Keefe; Adrian S Woolf; Helen M Stuart; William G Newman Journal: Clin Genet Date: 2019-09-11 Impact factor: 4.438