Heterogeneous AVPR2 gene mutations in congenital nephrogenic diabetes insipidus
- Univ. of Washington, Seattle, WA (United States)
Mutations in the AVPR2 gene encoding the receptor for arginine vasopressin in the kidney (V2 ADHR) have been reported in patients with congenital nephrogenic diabetes insipidus, a predominantly X-linked disorder of water homeostasis. The authors have used restriction-enzyme analysis and direct DNA sequencing of genomic PCR product to evaluate the AVPR2 gene in 11 unrelated affected males. Each patient has a different DNA sequence variation, and only one matches a previously reported mutation. Cosegregation of the variations with nephrogenic diabetes insipidus was demonstrated for two families, and a de novo mutation was accomplished in one family. All the variations predict frameshifts, truncations, or nonconservative amino acid substitutions in evolutionarily conserved positions in the V2 ADHR and related receptors. Of interest, a 28-bp deletion is found in one patient, while another, unrelated patient has a tandem duplication of the same 28-bp segment, suggesting that both resulted from the same unusual unequal crossing-over mechanism facilitated by 9-mer direct sequence repeats. Since the V2 ADHR is a member of the seven-transmembrane-domain, G-protein-coupled receptor superfamily, the loss-of-function mutations from this study and others provide important clues to the structure-function relationship of this and related receptors. 55 refs., 4 figs., 2 tabs.
- OSTI ID:
- 6811115
- Journal Information:
- American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 55:2; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
BODY
CHROMOSOMES
DISEASES
GENE MUTATIONS
HEREDITARY DISEASES
HETEROCHROMOSOMES
HOMEOSTASIS
HUMAN CHROMOSOMES
HUMAN X CHROMOSOME
HYDROGEN COMPOUNDS
KIDNEYS
MEMBRANE PROTEINS
MUTATIONS
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PROTEINS
RECEPTORS
WATER
X CHROMOSOME