Medical Genetics, IRCCS Casa Sollievo della Sofferenza Hospital, viale Padre Pio, 71013 San Giovanni Rotondo, FG, Italy.
Mol Genet Metab. 2012 Nov;107(3):548-52. doi: 10.1016/j.ymgme.2012.06.012. Epub 2012 Jun 26.
Autosomal dominant hypocalcemia (ADH) is an endocrine disorder caused by activating mutations of the calcium-sensing receptor (CASR) gene which plays a major role in maintaining calcium homeostasis. Biochemical features of ADH are hypocalcemia and hypercalciuria with inappropriately low levels of parathyroid hormone (PTH). We report on two four-generation families affected by ADH.
To identify mutations of CASR gene in subjects affected by familial idiopathic hypoparathyroidism. To perform functional assays of identified CASR variants by transient transfection on HEK293 cells.
We identified two CASR variants (Q681R and P221L): the Q681R variant was novel while the P221L had been previously published. Functional assays on the Q681R variant showed that it did not alter the whole expression nor the correct plasmamembrane localization, but enhanced the signaling function, increasing the sensitivity of the receptor as compared to the WT.
We report two activating CASR mutations in two families affected by ADH and the functional assays performed on the novel variant Q681R. Our work enlarged the spectrum of mutations of the CASR and contributed to a better elucidation of the protein function.
常染色体显性低钙血症（ADH）是一种由钙敏感受体（CASR）基因突变引起的内分泌疾病，该基因在维持钙稳态中起主要作用。ADH 的生化特征是低钙血症和高钙尿症，甲状旁腺激素（PTH）水平不适当降低。我们报告了两个受 ADH 影响的四代家族。
在受家族性特发性甲状旁腺功能减退症影响的个体中鉴定 CASR 基因的突变。通过瞬时转染 HEK293 细胞对鉴定的 CASR 变体进行功能测定。
我们鉴定了两种 CASR 变体（Q681R 和 P221L）：Q681R 变体是新的，而 P221L 先前已发表。对 Q681R 变体的功能测定表明，它没有改变整个表达或正确的质膜定位，但增强了信号转导功能，与 WT 相比，增加了受体的敏感性。
我们报告了两个受 ADH 影响的家族中的两种激活 CASR 突变，以及对新型 Q681R 变体进行的功能测定。我们的工作扩大了 CASR 突变谱，并有助于更好地阐明蛋白功能。
