Identification and functional analysis of novel calcium-sensing receptor gene mutation in familial hypocalciuric hypercalcemia.
Endocr J
; 57(9): 787-92, 2010.
Article
en En
| MEDLINE
| ID: mdl-20697181
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 Ca(2+) was characterized by transient transfection into human embryonic kidney (HEK) 293 cells and treatment with increasing extracellular Ca(2+) concentrations. HEK cells didn't activate intracellular signaling (MAPK activation) in response to increases of extracellular Ca(2+) 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 Ca(2+) caused FHH in patients and our study demonstrated the importance of Asp-190 participated in response to Ca(2+) in CASR.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores Sensibles al Calcio
/
Hipercalcemia
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Endocr J
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Japón