PMID- 17698911
OWN - NLM
STAT- MEDLINE
DCOM- 20080102
LR  - 20131121
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 92
IP  - 11
DP  - 2007 Nov
TI  - Molecular genetic analysis of the calcium sensing receptor gene in patients 
      clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic 
      variation and mutation spectrum in a Danish population.
PG  - 4373-9
AB  - CONTEXT: The autosomal dominantly inherited condition familial hypocalciuric 
      hypercalcemia (FHH) is characterized by elevated plasma calcium levels, relative 
      or absolute hypocalciuria, and normal to moderately elevated plasma PTH. The 
      condition is difficult to distinguish clinically from primary hyperparathyroidism 
      and is caused by inactivating mutations in the calcium sensing receptor (CASR) 
      gene. OBJECTIVE: We sought to define the mutation spectrum of the CASR gene in a 
      Danish FHH population and to establish genotype-phenotype relationships regarding 
      the different mutations. DESIGN AND PARTICIPANTS: A total of 213 subjects 
      clinically suspected to have FHH, and 121 subjects enrolled as part of a 
      family-screening program were studied. Genotype-phenotype relationships were 
      established in 66 mutation-positive index patients and family members. MAIN 
      OUTCOME MEASURES: We determined CASR gene mutations, and correlating levels of 
      plasma calcium (albumin corrected), ionized calcium (pH 7.4), and PTH were 
      measured. RESULTS: We identified 22 different mutations in 39 FHH families. We 
      evaluated data on circulating calcium and PTH for 11 different mutations, 
      representing a spectrum of clinical phenotypes, ranging from calcium 
      concentrations moderately above the upper reference limit, to calcium levels more 
      than 20% above the upper reference limit. Furthermore, the mean plasma PTH 
      concentration was within the normal range in eight of 11 studied mutations, but 
      mild to moderately elevated in families with the mutations p.C582Y, p.C582F, and 
      p.G553R. CONCLUSIONS: The present data add 19 novel mutations to the catalog of 
      inactivating CASR mutations and illustrate a variety of biochemical phenotypes in 
      patients with the molecular genetic diagnosis FHH.
FAU - Nissen, Peter H
AU  - Nissen PH
AD  - Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus Sygehus, 
      Tage Hansens gade 2, DK-8000 Aarhus C, Denmark. sci08phn@as.aaa.dk
FAU - Christensen, Signe E
AU  - Christensen SE
FAU - Heickendorff, Lene
AU  - Heickendorff L
FAU - Brixen, Kim
AU  - Brixen K
FAU - Mosekilde, Leif
AU  - Mosekilde L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070814
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Codon)
RN  - 0 (Parathyroid Hormone)
RN  - 0 (Receptors, Calcium-Sensing)
RN  - 9007-49-2 (DNA)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/*blood/*urine
MH  - Codon
MH  - Computational Biology
MH  - DNA/biosynthesis/genetics
MH  - Denmark/epidemiology
MH  - Gene Frequency
MH  - Genetic Variation
MH  - Humans
MH  - Hypocalcemia/blood/*genetics/urine
MH  - Linear Models
MH  - Molecular Biology
MH  - Mutation/*genetics
MH  - Parathyroid Hormone/blood
MH  - Phenotype
MH  - Receptors, Calcium-Sensing/*genetics
EDAT- 2007/08/19 09:00
MHDA- 2008/01/03 09:00
CRDT- 2007/08/19 09:00
PHST- 2007/08/19 09:00 [pubmed]
PHST- 2008/01/03 09:00 [medline]
PHST- 2007/08/19 09:00 [entrez]
AID - jc.2007-0322 [pii]
AID - 10.1210/jc.2007-0322 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2007 Nov;92(11):4373-9. doi: 10.1210/jc.2007-0322. Epub 
      2007 Aug 14.