title: A novel splicing mutation in the V2 vasopressin receptor.
abstract: In order to elucidate the molecular basis and the clinical characteristics of X-linked recessive nephrogenic diabetes insipidus (CNDI) in a kindred of Danish descent, we performed direct sequencing of the arginine vasopressin receptor 2 (AVPR2) gene in five members of the family, as well as clinical investigations comprising a fluid deprivation test and a 1-deamino-8-D-arginine-vasopressin (dDAVP) infusion test in the study subject and his mother. We found a highly unusual, novel, de novo 1447A-->C point mutation (gDNA), involving the invariable splice acceptor of the second intron of the gene in both the affected male (hemizygous) and his mother (heterozygous). This mutation is likely to cause aberrant splicing of the terminal intron of the gene, leading to a non-functional AVP receptor. The clinical studies were consistent with such a hypothesis, as the affected subject had a severe insensitivity to both the antidiuretic and the coagulation factors stimulatory actions of AVP and its analogue dDAVP. Direct sequencing of the AVPR2 is an accurate and rapid diagnostic tool for CNDI and early referral of patients for AVPR2 sequencing is therefore strongly suggested.
authors.affiliation: Department of Pediatrics, Aarhus University Hospital, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Kamperis
authors.forename: C
authors.initials: C
authors.lastname: Siggaard
authors.forename: T
authors.initials: T
authors.lastname: Herlin
authors.forename: E
authors.initials: E
authors.lastname: Nathan
authors.forename: J M
authors.initials: JM
authors.lastname: Hertz
authors.forename: S
authors.initials: S
authors.lastname: Rittig
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D002675:Child, Preschool; D003894:Deamino Arginine Vasopressin; D003718:Denmark; D018500:Diabetes Insipidus, Nephrogenic / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D017483:Receptors, Vasopressin / Q000737:chemistry / Q000235:genetics*; D014960:X Chromosome
chemical_list: D017483:Receptors, Vasopressin; D003894:Deamino Arginine Vasopressin