Institut National de la Santé et de la Recherche Médicale, Paris, France.
Pediatrics. 2012 Jun;129(6):e1626-30. doi: 10.1542/peds.2011-2507. Epub 2012 May 7.
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.
威廉姆斯-比伦综合征（WBS）是一种与不明原因高钙血症相关的神经发育障碍。该综合征是由染色体 7 上连续基因缺失引起的，包括一般转录因子 IIi 基因。一般转录因子 IIi 基因编码 TFII-I，它抑制瞬时受体电位 C3（TRPC3）通道在细胞表面的积累，TRPC3 通道参与淋巴细胞中的钙转运。我们描述了一例伴有高钙血症的 WBS 患者，其 TRPC3 表达异常。与对照患者相比，外周淋巴细胞中 TRPC3 的表达明显增加。为了研究 TRPC3 在钙稳态中的潜在作用，我们对主要钙调节组织的肠道和肾脏进行了特异性免疫染色。我们首次证明 TRPC3 在对照患者的正常消化上皮和肾小管中表达，而在 WBS 患者的肠道中过度表达。这些数据表明，WBS 中观察到的钙代谢异常可能归因于 TFII-I 杂合不足和随后的 TRPC3 过度表达，从而增加了肠道和肾脏的钙吸收。这一原始观察结果提示进一步研究 TRPC3 作为钙稳态的新型调节剂。
