PMID- 26386835
OWN - NLM
STAT- MEDLINE
DCOM- 20170310
LR  - 20191210
IS  - 1435-5604 (Electronic)
IS  - 0914-8779 (Linking)
VI  - 34
IP  - 6
DP  - 2016 Nov
TI  - Identification and functional analysis of a novel CaSR mutation in a family with 
      familial hypocalciuric hypercalcemia.
PG  - 662-667
AB  - The calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that plays an 
      essential role in maintaining calcium homeostasis. In the present study, we 
      analyzed the CaSR gene in a Korean family with familial hypocalciuric 
      hypercalcemia (FHH). Genetic studies were performed by direct sequence analysis 
      of the CaSR gene in genomic DNA obtained from peripheral leukocytes. A novel 
      heterozygous G to T substitution at nucleotide position 1711 in exon 6, resulting 
      in the G571W mutation, was identified in the CaSR gene in a 26-year-old female 
      with asymptomatic hypercalcemia, a low calcium/creatinine clearance ratio, and 
      normal intact parathyroid hormone. To study CaSR expression, the mutation was 
      introduced by site-directed mutagenesis into a wild-type (WT) CaSR-expressing 
      pCR3.1 vector, and COS-7 cells were transfected with either the WT or mutant 
      CaSR-containing vector. Transfected cells loaded with Fura-2/AM, a fluorescent 
      indicator of Ca(2+), were assessed for CaSR function by the change in 
      intracellular calcium [as measured by the 340 nm/380 nm fluorescence intensity 
      ratio (F340/F380)] made in response to challenge with extracellular Ca(2+). Both 
      WT and G571W cells had equivalent amounts of CaSR protein in the cell membrane. 
      However, after challenge with extracellular Ca(2+), cells transfected with G571W 
      CaSR responded with a lower F340/F380 ratio than those transfected with WT CaSR 
      and showed decreased sensitivity to extracellular Ca(2+) concentrations. The 
      G571W mutation had therefore impaired the CaSR function. In conclusion, we 
      identified a novel loss-of-function mutation, G571W, in the CaSR gene in a Korean 
      family with FHH.
FAU - Kim, Eun Sook
AU  - Kim ES
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Incheon St. Mary's Hospital, College of Medicine, The Catholic University of 
      Korea, 56 Dongsoo-ro, Bupyeong-gu, Incheon, 403-720, Republic of Korea.
FAU - Kim, Su Yeon
AU  - Kim SY
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Incheon St. Mary's Hospital, College of Medicine, The Catholic University of 
      Korea, 56 Dongsoo-ro, Bupyeong-gu, Incheon, 403-720, Republic of Korea.
FAU - Lee, Ji Young
AU  - Lee JY
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Incheon St. Mary's Hospital, College of Medicine, The Catholic University of 
      Korea, 56 Dongsoo-ro, Bupyeong-gu, Incheon, 403-720, Republic of Korea.
FAU - Han, Je Ho
AU  - Han JH
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Incheon St. Mary's Hospital, College of Medicine, The Catholic University of 
      Korea, 56 Dongsoo-ro, Bupyeong-gu, Incheon, 403-720, Republic of Korea.
FAU - Sohn, Tae Seo
AU  - Sohn TS
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Uijungbu St. Mary's Hospital, College of Medicine, The Catholic University of 
      Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, Republic of Korea. 
      imsts@catholic.ac.kr.
FAU - Son, Hyun Shik
AU  - Son HS
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Uijungbu St. Mary's Hospital, College of Medicine, The Catholic University of 
      Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, Republic of Korea.
FAU - Moon, Sung-Dae
AU  - Moon SD
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Incheon St. Mary's Hospital, College of Medicine, The Catholic University of 
      Korea, 56 Dongsoo-ro, Bupyeong-gu, Incheon, 403-720, Republic of Korea. 
      sungdaem@gmail.com.
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20150919
PL  - Japan
TA  - J Bone Miner Metab
JT  - Journal of bone and mineral metabolism
JID - 9436705
RN  - 0 (CASR protein, human)
RN  - 0 (Receptors, Calcium-Sensing)
RN  - SY7Q814VUP (Calcium)
RN  - Hypocalciuric hypercalcemia, familial, type 1
SB  - IM
MH  - Adult
MH  - Amino Acid Substitution
MH  - Animals
MH  - COS Cells
MH  - Calcium/metabolism
MH  - Chlorocebus aethiops
MH  - Family
MH  - Female
MH  - Gene Expression Regulation/genetics
MH  - Humans
MH  - Hypercalcemia/*congenital/genetics/metabolism
MH  - *Mutation, Missense
MH  - Receptors, Calcium-Sensing/biosynthesis/*genetics
MH  - Republic of Korea
OTO - NOTNLM
OT  - Autosomal dominant
OT  - Calcium-sensing receptor
OT  - Familial hypocalciuric hypercalcemia
EDAT- 2016/11/01 06:00
MHDA- 2017/03/11 06:00
CRDT- 2015/09/21 06:00
PHST- 2015/04/15 00:00 [received]
PHST- 2015/08/16 00:00 [accepted]
PHST- 2016/11/01 06:00 [pubmed]
PHST- 2017/03/11 06:00 [medline]
PHST- 2015/09/21 06:00 [entrez]
AID - 10.1007/s00774-015-0713-z [pii]
AID - 10.1007/s00774-015-0713-z [doi]
PST - ppublish
SO  - J Bone Miner Metab. 2016 Nov;34(6):662-667. doi: 10.1007/s00774-015-0713-z. Epub 
      2015 Sep 19.