Heterogeneous AVPR2 gene mutations in congenital nephrogenic diabetes insipidus
Abstract
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.
- Authors:
-
- Univ. of Washington, Seattle, WA (United States)
- Publication Date:
- OSTI Identifier:
- 6811115
- Resource Type:
- Journal Article
- Journal Name:
- American Journal of Human Genetics; (United States)
- Additional Journal Information:
- Journal Volume: 55:2; Journal ID: ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; KIDNEYS; HEREDITARY DISEASES; RECEPTORS; GENE MUTATIONS; WATER; HOMEOSTASIS; HUMAN X CHROMOSOME; BODY; CHROMOSOMES; DISEASES; HETEROCHROMOSOMES; HUMAN CHROMOSOMES; HYDROGEN COMPOUNDS; MEMBRANE PROTEINS; MUTATIONS; ORGANIC COMPOUNDS; ORGANS; OXYGEN COMPOUNDS; PROTEINS; X CHROMOSOME; 550400* - Genetics
Citation Formats
Wildin, R S, Antush, M J, Bennett, R L, Schoof, J M, and Scott, C R. Heterogeneous AVPR2 gene mutations in congenital nephrogenic diabetes insipidus. United States: N. p., 1994.
Web.
Wildin, R S, Antush, M J, Bennett, R L, Schoof, J M, & Scott, C R. Heterogeneous AVPR2 gene mutations in congenital nephrogenic diabetes insipidus. United States.
Wildin, R S, Antush, M J, Bennett, R L, Schoof, J M, and Scott, C R. 1994.
"Heterogeneous AVPR2 gene mutations in congenital nephrogenic diabetes insipidus". United States.
@article{osti_6811115,
title = {Heterogeneous AVPR2 gene mutations in congenital nephrogenic diabetes insipidus},
author = {Wildin, R S and Antush, M J and Bennett, R L and Schoof, J M and Scott, C R},
abstractNote = {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.},
doi = {},
url = {https://www.osti.gov/biblio/6811115},
journal = {American Journal of Human Genetics; (United States)},
issn = {0002-9297},
number = ,
volume = 55:2,
place = {United States},
year = {Mon Aug 01 00:00:00 EDT 1994},
month = {Mon Aug 01 00:00:00 EDT 1994}
}