title: Williams-Beuren syndrome hypercalcemia: is TRPC3 a novel mediator in calcium homeostasis?
abstract: Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder associated with hypercalcemia of unknown origin. This syndrome results from the deletion of contiguous genes on chromosome 7, including the general transcription factor IIi gene. The general transcription factor IIi gene encodes TFII-I, which suppresses cell-surface accumulation of transient receptor potential C3 (TRPC3) channels, involved in calcium transport in lymphocytes. We describe the case of a patient with WBS with hypercalcemia associated with abnormal TRPC3 expression. Analysis of peripheral lymphocytes revealed a sharp increase in TRPC3 expression, compared with control patients. To investigate the potential role of TRPC3 in calcium homeostasis, we performed specific immunostaining on the intestine and the kidney, major calcium-regulating tissues. We provide the first demonstration that TRPC3 is expressed in normal digestive epithelium and renal tubules in control patients, and overexpressed in the intestine in the patient with WBS. Taken together, these data suggest that calcium metabolism abnormalities observed in WBS may be attributable to TFII-I haploinsufficiency and subsequent TRPC3 overexpression, thereby increasing both digestive and renal calcium absorption. This original observation prompts further investigation of TRPC3 as a novel actor of calcium homeostasis.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Paris, France. emmanuel.letavernier@tnn.aphp.fr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Letavernier
authors.forename: Anita
authors.initials: A
authors.lastname: Rodenas
authors.forename: Dominique
authors.initials: D
authors.lastname: Guerrot
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Haymann
mesh_terms: D002118:Calcium / Q000502:physiology*; D057895:Haploinsufficiency / Q000235:genetics; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D006934:Hypercalcemia / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D019473:Transcription Factors, TFII / Q000235:genetics; D018980:Williams Syndrome / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*
chemical_list: D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D019473:Transcription Factors, TFII; D002118:Calcium