A Novel Activating Mutation in Calcium-Sensing Receptor Gene Associated with a Family of Autosomal Dominant Hypocalcemia1
| Autor: | Ryo Okazaki, Miho Ajima, Seiji Fukumoto, Junko Miki, Masami Nakatsu, Koshi Tanaka, Noriko Chikatsu, Yasuo Totsuka, Yasuhiro Takeuchi, Masanobu Arai, Toshiro Fujita |
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| Rok vydání: | 1999 |
| Předmět: |
Proband
endocrine system medicine.medical_specialty Mutation Endocrinology Diabetes and Metabolism Biochemistry (medical) Clinical Biochemistry HEK 293 cells Mutant Biology medicine.disease_cause Biochemistry Endocrinology Polymorphism (computer science) Internal medicine medicine Missense mutation Calcium-sensing receptor Gene hormones hormone substitutes and hormone antagonists |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 84:363-366 |
| ISSN: | 1945-7197 0021-972X |
| Popis: | Autosomal dominant hypocalcemia (ADH), caused by activating mutations of the calcium-sensing receptor (CaSR), is characterized by hypocalcemia with an inappropriately low concentration of PTH. Among 11 missense mutations of CaSR reported to date in patients with ADH or sporadic hypocalcemia, functional properties of 8 mutant CaSRs were characterized. Here, we describe a novel mutation of CaSR and its functional property in a family with ADH. The 41-yr-old male proband had asymptomatic hypocalcemia with a history of recurrent nephrolithiasis. His father had asymptomatic hypocalcemia, but his mother was normocalcemic. PCR-single strand conformation polymorphism and sequencing revealed that both the proband and the father had a novel heterozygous mutation in CaSR gene that causes lysine to asparagine substitution at codon 47 (K47N), which is in the extracellular domain of CaSR, like 6 of 11 known activating mutations. Using HEK293 cells transfected with wild-type or K47N CaSR complementary DNA, the intracell... |
| Databáze: | OpenAIRE |
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