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Identification and functional analysis of novel calcium-sensing receptor gene mutation in familial hypocalciuric hypercalcemia

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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)

Submitter: 小池 隆夫

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