title: Novel gain of function mutations of the calcium-sensing receptor in two patients with PTH-deficient hypocalcemia.
abstract: Among 15 patients with PTH-deficient idiopathic hypocalcemia, we found two novel missense mutations in the calcium-sensing receptor (CaSR). Patient 1, who developed severe hypocalcemia (5.0 mg/dL) and seizures after birth, had a heterozygous de novo missense mutation in the transmembrane domain (A844P). The patient is currently receiving a minimum dose of 1alpha-OHD(3) (0.5 microg/day) to maintain the serum calcium level at 6 mg/dL and thus prevent seizures. Patient 2 had asymptomatic hypocalcemia (7.5 mg/dL) and also had a heterozygous missense mutation in the extracellular domain (E228G). These findings suggest that gene analysis of CaSR should be performed in patients with idiopathic hypocalcemia, particularly when it occurs in the neonatal period.
authors.affiliation: Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, Tokyo.
authors.forename: Kishiko
authors.initials: K
authors.lastname: Nakajima
authors.forename: Kazuko
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Hironari
authors.initials: H
authors.lastname: Kimura
authors.forename: Kazue
authors.initials: K
authors.lastname: Takano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Kanji
authors.initials: K
authors.lastname: Sato
mesh_terms: D000293:Adolescent; D000328:Adult; D002118:Calcium / Q000097:blood; D002648:Child; D005260:Female; D006579:Heterozygote; D006801:Humans; D006996:Hypocalcemia / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D007011:Hypoparathyroidism / Q000150:complications* / Q000188:drug therapy; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D044169:Receptors, Calcium-Sensing / Q000235:genetics*; D012640:Seizures / Q000209:etiology; D055815:Young Adult
chemical_list: D044169:Receptors, Calcium-Sensing; D002118:Calcium