Genetic analysis of an unusual family with hypocalciuric hypercalcemia

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134036

Janicic, N; Pausova, Z; Hendy, G N ^[1]

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1. McGill Univ., Montreal (Canada); and others

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disorder characterized by modest elevation of serum calcium concentration, relative hypocalciuria and inappropriately normal parathyroid hormone levels. The disease has been mapped to chromosome 3q in several families, and in one other family linkage to chromosome 19p has been demonstrated. We have analyzed leukocyte DNA from 8 members of the three-generation FHH family, four of whom were affected. This family is unusual in that two of the affected members have hypercalciuria rather than hypocalciuria. In order to localize the mutant gene, we carried out studies using 8 genetic markers for chromosome region 3q11.2-24 and 1 marker for 19p13.3. These markers were used to detect DNA polymorphisms by polymerase chain reaction (PCR) amplification of microsatellite tandem repeats. In all affected individuals the disease locus cosegregated with the same haplotype which was derived by analysis with the 4 informative markers (D3S1215-D3S1267-D3S1269-D3S47) for chromosome 3q with one recombinant only with marker D3S47. The disease locus did not segregate with the genotype obtained with the informative marker (D19S247) for chromosome 19p. Recently, the parathyroid calcium receptor gene was mapped to chromosome 3 and mutations in exons 3 (R186E, E298K) and 6 (R796W) of the gene were identified in some patients with FHH. We have sequenced exons 3 and 6 in our family, but we did not find the previously identified mutations. It is likely therefore that mutations will be found scattered throughout the calcium receptor gene in different FHH kindreds.

• OSTI ID: 134036
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL MARKERS
CALCIUM
DNA SEQUENCING
DOMINANT MUTATIONS
GENE MUTATIONS
GENES
GENETIC MAPPING
GENOTYPE
HEREDITARY DISEASES
HUMAN CHROMOSOME 19
HUMAN CHROMOSOME 3
METABOLIC DISEASES
PARATHORMONE
PATIENTS
POLYMERASE CHAIN REACTION