Insertion of an Alu sequence in the Ca{sup 2+}-sensing receptor gene in familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism

Journal Article · Sat Apr 01 04:00:00 EST 1995 · American Journal of Human Genetics

OSTI ID:70424

Janicic, N; Pausova, Z; Hendy, G N ^[1]; Cole, D E.C. ^[2]

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1. McGill Univ. and Royal Victoria Hospital, Montreal (Canada)
2. Univ. of Toronto and Banting Institute (Canada)

Missense mutations in the calcium-sensing receptor (CaR) gene have previously been identified in patients with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyoidism (NSHPT). We studied family members of a Nova Scotian deme expressing both FHH and NSHPT and found, by PCR amplification of CaR gene exons, that FHH individuals were heterozygous and NSHPT individuals were homozygous for an abnormally large exon 7. This is due to an insertion at codon 877 of an Alu-repetitive element of the predicted-variant/human-specific-1 subfamily. It is in the opposite orientation to the CaR gene and contains an exceptionally long poly(A) tract. Stop signals are introduced in all reading frames within the Alu sequence, leading to a predicted shortened mutant CaR protein. The loss of the majority of the CaR carboxyl-terminal intracellular domain would dramatically impair its signal transduction capability. Identification of the specific mutation responsible for the FHH/NSHPT phenotype in the community will allow rapid testing of at-risk individuals. 42 refs., 5 figs.

• OSTI ID: 70424
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 4 Vol. 56; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CALCIUM
CHROMOSOMAL ABERRATIONS
DOMINANT MUTATIONS
GENE MUTATIONS
GENES
HEREDITARY DISEASES
HUMAN CHROMOSOMES
METABOLISM
PATIENTS
PHENOTYPE
POLYMERASE CHAIN REACTION
PROTEINS