title: Mutations of calcium-sensing receptor gene: two novel mutations and overview of impact on calcium homeostasis.
abstract: OBJECTIVE
  Genetic disorders of calcium metabolism arise in a familial or sporadic setting. The calcium-sensing receptor (CASR) plays a key role in maintaining calcium homeostasis and study of the CASR gene can be clinically useful in determining etiology and appropriate therapeutic approaches. We report two cases of novel CASR gene mutations that illustrate the varying clinical presentations and discuss these in terms of the current understanding of CASR function.
  
  
  METHODS
  A 16-year-old patient had mild hypercalcemia associated with low-normal urinary calcium excretion and normal-to-high parathyroid hormone (PTH) levels. Because of negative family history, familial hypocalciuric hypercalcemia was originally excluded. The second patient was a 54-year-old man with symptomatic hypocalcemia, hyperphosphatemia, low PTH, and mild hypercalciuria. Familial investigation revealed the same phenotype in the patient's sister. The coding region of the CASR gene was sequenced in both probands and their available first-degree relatives.
  
  
  RESULTS
  The first patient had a novel heterozygous inactivating CASR mutation in exon 4, which predicted a p.A423K change; genetic analysis was negative in the parents. The second patient had a novel heterozygous activating CASR mutation in exon 6, which predicted a p.E556K change; the affected sister of the proband was also positive.
  
  
  CONCLUSIONS
  We reported two novel heterozygous mutations of the CASR gene, an inactivating mutation in exon 4 and the first activating mutation reported to date in exon 6. These cases illustrate the importance of genetic testing of CASR gene to aid correct diagnosis and to assist in clinical management.
authors.affiliation: Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, 4000 Liège, Belgium.
authors.forename: Elena
authors.initials: E
authors.lastname: Livadariu
authors.forename: Renata S
authors.initials: RS
authors.lastname: Auriemma
authors.forename: Catherine
authors.initials: C
authors.lastname: Rydlewski
authors.forename: Silvia
authors.initials: S
authors.lastname: Vandeva
authors.forename: Etienne
authors.initials: E
authors.lastname: Hamoir
authors.forename: Maria C
authors.initials: MC
authors.lastname: Burlacu
authors.forename: Sylvie
authors.initials: S
authors.lastname: Maweja
authors.forename: Anne S
authors.initials: AS
authors.lastname: Thonnard
authors.forename: Daniela
authors.initials: D
authors.lastname: Betea
authors.forename: Gilbert
authors.initials: G
authors.lastname: Vassart
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Daly
authors.forename: Albert
authors.initials: A
authors.lastname: Beckers
mesh_terms: D000293:Adolescent; D002118:Calcium / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005260:Female; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006801:Humans; D006934:Hypercalcemia / Q000235:genetics; D006996:Hypocalcemia / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D010375:Pedigree; D044169:Receptors, Calcium-Sensing / Q000235:genetics*; D035781:Siblings
chemical_list: D044169:Receptors, Calcium-Sensing; D002118:Calcium