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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
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Identification and functional analysis of novel calcium-sensing receptor gene mutation in familial hypocalciuric hypercalcemia
| Title: | Identification and functional analysis of novel calcium-sensing receptor gene mutation in familial hypocalciuric hypercalcemia |
| Authors: | Nanjo, Kazuhiro Browse this author | | Nagai, So Browse this author →KAKEN DB | | Shimizu, Chikara Browse this author →KAKEN DB | | Tajima, Toshihiro Browse this author →KAKEN DB | | Kondo, Takuma Browse this author | | Miyoshi, Hideaki Browse this author →KAKEN DB | | Yoshioka, Narihito Browse this author →KAKEN DB | | Koike, Takao Browse this author →KAKEN DB |
| Keywords: | Calcium-sensing receptor | | Familial hypocalciuric hypercalcemia | | MAPK signaling pathway |
| Issue Date: | Sep-2010 |
| Publisher: | Japan Endocrine Society |
| Journal Title: | Endocrine journal |
| Volume: | 57 |
| Issue: | 9 |
| Start Page: | 787 |
| End Page: | 792 |
| Publisher DOI: | 10.1507/endocrj.K10E-178 |
| Abstract: | Familial hypocalciuric hypercalcemia (FHH) is a benign disorder with heterozygous inactivating mutations in the calcium-sensing receptor (CASR) gene. The present study describes the identification and functional analysis of a novel CASR gene mutation leading to FHH. The proband is a 33-yr-old woman (Ca 11.0 mg/dL, intact-PTH 68 pg/mL, FECa 0.17 %). Leukocyte DNA was isolated in four family members and a novel heterozygous mutation (D190G, GAT>GGT) in exon 4 of CASR gene was identified by direct sequence analysis. The mutant CASR expression vector was constructed by mutagenesis procedure and its response to Ca2+ was characterized by transient transfection into human embryonic kidney (HEK) 293 cells and treatment with increasing extracellular Ca2+ concentrations. HEK cells didn't activate intracellular signaling (MAPK activation) in response to increases of extracellular Ca2+ concentrations when the mutant receptor was expressed normally at the cell surface. The novel heterozygous mutation (D190G) identified in the present study showed that the reduction of activity of CASR to extracellular Ca2+ caused FHH in patients and our study demonstrated the importance of Asp-190 participated in response to Ca2+ in CASR. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/67200 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 小池 隆夫
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