Familial hypocalciuric hypercalcemia associated with mutation in the human Ca{sup 2+}-sensing receptor gene

Journal Article · Fri Sep 01 04:00:00 EDT 1995 · Journal of Clinical Endocrinology and Metabolism

DOI:https://doi.org/10.1210/jc.80.9.2594· OSTI ID:430223

Aida, Kaoru; Koishi, Sawako; Inoue, Masaharu ^[1]

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1. Univ. of Yamanashi Medical School, Yamanashi (Japan); and others

Familial hypocalciuric hypercalcemia (FHH) is generally characterized by lifelong hypercalcemia without hypercalciuria and is inherited in an autosomal dominant manner. Affected individuals show abnormal parathyroid and renal responses to changes in the extracellular calcium concentration. A Japanese FHH family was screened for mutations in the Ca{sup 2+} -sensing receptor gene by the polymerase chain reaction and single strand conformation polymorphism. The proband with hypercalcemia showed an abnormal pattern in exon 1 of the gene, whereas her two sisters with normocalcemia showed a normal pattern. The consanguineous parents with borderline serum calcium concentrations showed both patterns. Nucleotide sequence analysis identified a G{yields}C point mutation at nucleotide 118 that resulted in the conversion of the normal codon for proline into a codon for alanine at amino acid 40 (numbered according to the bovine complementary DNA). The proband was homozygous for the mutation, and the parents were heterozygous. These results imply that this mutation in the human Ca{sup 2+}-sensing receptor gene causes FHH and that the dosage of the gene defect determines disease phenotype. 33 refs., 4 figs., 1 tab.

• OSTI ID: 430223
• Journal Information: Journal of Clinical Endocrinology and Metabolism, Journal Name: Journal of Clinical Endocrinology and Metabolism Journal Issue: 9 Vol. 80; ISSN JCEMAZ; ISSN 0021-972X
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
AMINO ACIDS
CALCIUM
CODONS
DNA SEQUENCING
DOMINANT MUTATIONS
EXONS
GENE MUTATIONS
GENES
GENETICS
HEREDITARY DISEASES
METABOLIC DISEASES
NUCLEOTIDES
PATIENTS
PHENOTYPE
POLYMERASE CHAIN REACTION
RECEPTORS