Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus
Abstract
Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant disorder characterized by progressive postnatal deficiency of arginine vasopressin as a result of mutation in the gene that encodes the hormone. To determine the extent of mutations in the coding region that produce the phenotype, we studied members of 17 unrelated kindreds with the disorder. We sequenced all 3 exons of the gene by using a rapid, direct dye-terminator method and found the causative mutation in each kindred. In four kindreds, the mutations were each identical to mutations described in other affected families. In the other 13 kindreds each mutation was unique. There were two missense mutations that altered the cleavage region of the signal peptide, seven missense mutations in exon 2, which codes for the conserved portion of the protein, one nonsense mutation in exon 2, and three nonsense mutations in exon 3. These findings, together with the clinical features of FNDI, suggest that each of the mutations exerts an effect by directing the production of a pre-prohormone that cannot be folded, processed, or degraded properly and eventually destroys vasopressinergic neurons. 63 refs., 5 figs., 6 tabs.
- Authors:
-
- Aahus Univ. Hospital and Faculty of Health Sciences (Denmark); and others
- Publication Date:
- OSTI Identifier:
- 232378
- Resource Type:
- Journal Article
- Journal Name:
- American Journal of Human Genetics
- Additional Journal Information:
- Journal Volume: 58; Journal Issue: 1; Other Information: PBD: Jan 1996
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 55 BIOLOGY AND MEDICINE, BASIC STUDIES; GENES; GENE MUTATIONS; DNA SEQUENCING; HORMONES; STRUCTURE-ACTIVITY RELATIONSHIPS; PATIENTS; HEREDITARY DISEASES; PHENOTYPE; METABOLIC DISEASES; VASOPRESSIN; NUCLEOTIDES; AMINO ACIDS; DOMINANT MUTATIONS; GENETICS; EXONS
Citation Formats
Rittig, S, Siggaard, C, and Pedersen, E B. Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus. United States: N. p., 1996.
Web.
Rittig, S, Siggaard, C, & Pedersen, E B. Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus. United States.
Rittig, S, Siggaard, C, and Pedersen, E B. 1996.
"Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus". United States.
@article{osti_232378,
title = {Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus},
author = {Rittig, S and Siggaard, C and Pedersen, E B},
abstractNote = {Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant disorder characterized by progressive postnatal deficiency of arginine vasopressin as a result of mutation in the gene that encodes the hormone. To determine the extent of mutations in the coding region that produce the phenotype, we studied members of 17 unrelated kindreds with the disorder. We sequenced all 3 exons of the gene by using a rapid, direct dye-terminator method and found the causative mutation in each kindred. In four kindreds, the mutations were each identical to mutations described in other affected families. In the other 13 kindreds each mutation was unique. There were two missense mutations that altered the cleavage region of the signal peptide, seven missense mutations in exon 2, which codes for the conserved portion of the protein, one nonsense mutation in exon 2, and three nonsense mutations in exon 3. These findings, together with the clinical features of FNDI, suggest that each of the mutations exerts an effect by directing the production of a pre-prohormone that cannot be folded, processed, or degraded properly and eventually destroys vasopressinergic neurons. 63 refs., 5 figs., 6 tabs.},
doi = {},
url = {https://www.osti.gov/biblio/232378},
journal = {American Journal of Human Genetics},
number = 1,
volume = 58,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 1996},
month = {Mon Jan 01 00:00:00 EST 1996}
}