title: New mutation in the CASR gene in a family with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT).
abstract: A loss of calcium-sensing receptor (CASR) function due to inactivating mutations can cause familial hypocalciuric hypercalcemia (FHH) or neonatal severe hyperparathyroidism (NSHPT). NSHPT represents the most severe expression of FHH and courses as a life-threatening condition. The aim of this study was to identify and characterize a CASR mutation in a female infant brought to the health service due to dehydration, apathy, lack of breast feeding and severe hypercalcemia. Molecular analysis was performed on genomic DNA of the index case and her parents. A novel homozygous mutation (p.E519X) in CASR was identified in the proband; both mother and father had the same mutation in heterozygous state, confirming their FHH condition. The mutation results in a truncated and inactive protein due to the lack of transmembrane and intracellular domains. The identification of this novel CASR gene mutation established the basis of hypercalcemia in this family and allowed a genetic counseling.
authors.affiliation: Laboratory of Molecular Genetics and Hormones, Division of Endocrinology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Luiza Souza
authors.initials: LS
authors.lastname: Rodrigues
authors.forename: Ana Carolina Arias
authors.initials: AC
authors.lastname: Cáu
authors.forename: Luciane Zgoda
authors.initials: LZ
authors.lastname: Bussmann
authors.forename: Gabriela
authors.initials: G
authors.lastname: Bastida
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Brunetto
authors.forename: Pedro Henrique Silveira
authors.initials: PH
authors.lastname: Corrêa
authors.forename: Regina Matsunaga
authors.initials: RM
authors.lastname: Martin
mesh_terms: D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000151:congenital* / Q000235:genetics; D006961:Hyperparathyroidism / Q000235:genetics* / Q000601:surgery; D007223:Infant; D007231:Infant, Newborn; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D044169:Receptors, Calcium-Sensing / Q000235:genetics*; D012008:Recurrence
chemical_list: C095550:CASR protein, human; D044169:Receptors, Calcium-Sensing