title: Two novel missense mutations in calcium-sensing receptor gene associated with neonatal severe hyperparathyroidism.
abstract: Familial hypocalciuric hypercalcemia (FHH) is characterized by lifelong asymptomatic hypercalcemia without PTH hypersecretion and is inherited as an autosomal dominant trait with near 100% penetrance. In contrast, neonatal severe hyperparathyroidism (NSHPT) is a life-threatening disorder characterized by marked hypercalcemia and PTH hypersecretion. FHH/NSHPT results from inactivating mutations of the human calcium-sensing receptor (Casr) gene on chromosome 3q13.3-24. Nearly 30 different mutations of the Casr gene associated with FHH/NSHPT have been reported previously. In this report, genetic analysis of 1 Japanese NSHPT family revealed 2 novel mutations at codon 185 (CGA-->TGA/Arg-->Ter) in exon 4 of the Casr gene and at codon 670 (GGG-->GAG/Gly-->Glu) in exon 7. The Arg185Ter change was shown to occur in the proband's unaffected father and paternal grandmother as well as in the proband. The other mutation in exon 7 was shown in the proband's unaffected mother of Philippine origin as well as in the proband. This family is the first case of manifestation of more than 1 mutation in a proband's chromosomes; 1 mutation was obtained from the unaffected father, and the other was from the unaffected mother. Our observations have given us important keys to help elucidate the structure-function relationships of the Casr.
authors.affiliation: Department of Pediatrics, Okayama University Medical School, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Tsuzuki
authors.forename: M
authors.initials: M
authors.lastname: Tsuyuki
authors.forename: H
authors.initials: H
authors.lastname: Igaki
authors.forename: Y
authors.initials: Y
authors.lastname: Ichinose
authors.forename: K
authors.initials: K
authors.lastname: Aya
authors.forename: N
authors.initials: N
authors.lastname: Nishioka
authors.forename: Y
authors.initials: Y
authors.lastname: Seino
mesh_terms: D001120:Arginine / Q000235:genetics; D001322:Autoanalysis; D001483:Base Sequence; D003062:Codon; D005260:Female; D005998:Glycine / Q000235:genetics; D006801:Humans; D006934:Hypercalcemia / Q000235:genetics; D006961:Hyperparathyroidism / Q000235:genetics*; D007231:Infant, Newborn; D007564:Japan; D009154:Mutation; D010281:Parathyroid Hormone / Q000378:metabolism; D010375:Pedigree; D016133:Polymerase Chain Reaction; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D003062:Codon; D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D001120:Arginine; D005998:Glycine