title: A novel mutation of the calcium-sensing receptor gene in a Greek family from Nisyros.
abstract: OBJECTIVE
  Inactivating mutations of the calcium-sensing receptor (CASR) gene cause familial hypocalciuric hypercalcaemia (FHH). Here we report three siblings with FHH caused by a novel mutation in the CASR.
  
  
  METHODS
  The case subject was a 60-year-old patient referred because of mild hypercalcaemia, increased PTH levels and persistently low calcium/creatinine ratio. FHH was suspected and a family biochemical and genetic analysis was performed.
  
  
  RESULTS
  Sequencing of the CASR gene revealed a frameshift mutation (Val258Arg) in the extracellular domain of the CASR that creates a premature 46 amino acids stop codon which leads to a truncated protein that might affect its function. This heterozygous loss-of-function mutation in the CaSR gene causes reduced CaSR sensing ability resulting in the clinical manifestation of FHH.
  
  
  CONCLUSIONS
  We hereby report the identification of a novel heterozygous loss-of-function mutation of the CASR gene in a Greek family from Nisyros island. Functional studies are needed to clarify the exact role of this mutation in CASR activity.
authors.affiliation: First Endocrine Department, Alexandra Hospital, Athens, Greece.
authors.forename: Evaggelia
authors.initials: E
authors.lastname: Zapanti
authors.affiliation: First Department of Internal Medicine, Laikon General Hospital, Athens University School of Medicine, Athens, Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Polonifi
authors.affiliation: First Department of Internal Medicine, Laikon General Hospital, Athens University School of Medicine, Athens, Greece.
authors.forename: Michalis
authors.initials: M
authors.lastname: Kokkinos
authors.affiliation: First Department of Internal Medicine, Laikon General Hospital, Athens University School of Medicine, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Boutzios
authors.affiliation: First Endocrine Department, Alexandra Hospital, Athens, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Kassi
authors.affiliation: Department of Biological Chemistry, Medical School, University of Athens, Athens, Greece.
authors.forename: Narjes
authors.initials: N
authors.lastname: Nasiri Ansari
authors.affiliation: Department of Biological Chemistry, Medical School, University of Athens, Athens, Greece.
authors.forename: Eva
authors.initials: E
authors.lastname: Kassi
authors.affiliation: First Department of Internal Medicine, Laikon General Hospital, Athens University School of Medicine, Athens, Greece.
authors.forename: Aris
authors.initials: A
authors.lastname: Polyzos
mesh_terms: D000368:Aged; D002118:Calcium / Q000378:metabolism; D005260:Female; D006115:Greece; D006801:Humans; D006934:Hypercalcemia / Q000151:congenital* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D044169:Receptors, Calcium-Sensing / Q000235:genetics*
chemical_list: C095550:CASR protein, human; D044169:Receptors, Calcium-Sensing; D002118:Calcium