title: A novel mutation (E767K) in the second extracellular loop of the calcium sensing receptor in a family with autosomal dominant hypocalcemia.
abstract: Autosomal dominant hypocalcemia resulting from gain-of-function mutations of the calcium sensing receptor (CASR) is a rare familial disorder that can become evident at any age. We report a novel mutation (E767K) of the CASR in a family with autosomal dominant hypocalcemia. Ten members of the family had a history of hypocalcemia. The index case exhibited marked hypocalcemia and seizures in the newborn period, while her father who also has hypocalcemia, was largely asymptomatic except for a myocardial infarction-like event at 21 years of age, a new presentation of the disorder. The E767K mutation, which resides in the second extracellular loop adjacent to the fifth transmembrane domain, co-segregated with hypocalcemia in these two individuals. Both subjects are heterozygous for the mutation. The proband is also heterozygous for the previously reported CASR polymorphism of G990R in the intracellular domain, while her father is homozygous. The co-segregation of this naturally occurring mutation with autosomal dominant hypocalcemia supports the previously reported experimental model in which it was proposed that the three acidic residues (767, 758, and 759) in exo-loop 2 in CASR help maintain an inactive conformation of the receptor.
authors.affiliation: Division of Pediatric Endocrinology, The University of North Carolina at Chapel Hill, NC 27599, USA. uckuna@yahoo.com
authors.forename: Ayşin
authors.initials: A
authors.lastname: Uçkun-Kitapçi
authors.forename: Louis E
authors.initials: LE
authors.lastname: Underwood
authors.forename: Jihui
authors.initials: J
authors.lastname: Zhang
authors.forename: Billie
authors.initials: B
authors.lastname: Moats-Staats
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005500:Follow-Up Studies; D005799:Genes, Dominant / Q000235:genetics*; D006801:Humans; D006996:Hypocalcemia / Q000235:genetics* / Q000473:pathology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D044169:Receptors, Calcium-Sensing / Q000235:genetics*
chemical_list: D044169:Receptors, Calcium-Sensing; D004247:DNA