title: Two novel mutations in the aquaporin-2 and the vasopressin V2 receptor genes in patients with congenital nephrogenic diabetes insipidus.
abstract: The vasopressin V2 receptor (V2R) and the aquaporin-2 genes of two unrelated male patients with congenital nephrogenic diabetes insipidus were analyzed. The V2R gene of the patient of family 1 had the wild-type sequence. Consequently, the coding region of the aquaporin-2 gene including the exon-intron junctions was sequenced. A novel G to T transversion at codon 202, predictive of an exchange of tryptophan 202 by cysteine, was identified. As the mutation occurs at G-1 of the 5' splice donor site of intron 3, aberrant splicing is also likely. The mutation involves one of the supposed water pore-forming loops. Therefore, both aberrant splicing and amino acid substitution are likely to result in a functionally defective protein. Sequencing of the complete V2R gene of the male patient of family 2 revealed a novel single-base deletion at codon 310 (delta C1001), shifting the reading frame to give an altered amino acid sequence beginning at codon 311. The mutation is unique in predicting a C-terminally extended protein (termination after codon 434 in the mutant receptor instead of codon 371 in the wild-type). The deduced mutant protein is likely to be nonfunctional since the amino acid sequence of the seventh transmembrane domain and the C-terminus is altered.
authors.affiliation: Rudolf-Buchheim-Institut für Pharmakologie, Justus-Liebig-Universität Giessen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Oksche
authors.forename: A
authors.initials: A
authors.lastname: Möller
authors.forename: J
authors.initials: J
authors.lastname: Dickson
authors.forename: W
authors.initials: W
authors.lastname: Rosendahl
authors.forename: W
authors.initials: W
authors.lastname: Rascher
authors.forename: D G
authors.initials: DG
authors.lastname: Bichet
authors.forename: W
authors.initials: W
authors.lastname: Rosenthal
mesh_terms: D000595:Amino Acid Sequence; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D004252:DNA Mutational Analysis; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017483:Receptors, Vasopressin / Q000235:genetics*; D015183:Restriction Mapping
chemical_list: C496023:AQP2 protein, human; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D007473:Ion Channels; D017483:Receptors, Vasopressin