Identification and characterization of D410E, a novel mutation in the loop 3 domain ofCASR, in autosomal dominant hypocalcemia and a therapeutic approach using a novel calcilytic,AXT914

• DOI: 10.1111/cen.12056
• Publication Date: 2012-09-25T22:56:36Z
• Authors: So Young Park; Hee‐Chang Mun; Young Sil Eom; Hae Lim Baek; Tae Sik Jung; Chul Hoon Kim; Suntaek Hong; Sihoon Lee
• Keywords: Adult; Male; Mitogen-Activated Protein Kinase 1; 0301 basic medicine; Mitogen-Activated Protein Kinase 3; Hypocalcemia; Middle Aged; 03 medical and health sciences; HEK293 Cells; Mutation; Humans; Female; Phosphorylation; Receptors, Calcium-Sensing

Activating mutations of the calcium-sensing receptor (CASR) gene are associated with autosomal dominant hypocalcemia (ADH) characterized by benign hypocalcemia, inappropriately low (PTH) levels and mostly hypercalciuria. Herein, we report a novel activating mutation in CASR Korean family ADH.The was sequenced patient ADH. The identified were also evaluated patient's members PCR-based sequencing. For functional studies, examined phosphorylation ERK1/2. In addition, intracellular Ca(2+) mobilization effects calcilytic, AXT914 measured using fluorophore Fura-2 dye.Direct sequencing analysis showed that proband her daughter possess c.1230T>A, resulting D410E missense on exon 4 gene. Escalation extracellular concentration resulted stronger ERK1/2 higher HEK293 cells expressing mutant CASR, compared wild-type CASR. increase signalling via successively blunted treatment AXT914.Over 60 have been to cause ADH so far. Here, add one more causes (D410E) occurred loop 3 region where its function believed be little importance; therefore, this may interest. Further clinical study will needed validate effectiveness calcilytics vivo.