title: A Null mutation in the vasopressin V2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus in the Hopewell kindred.
abstract: Congenital nephrogenic diabetes insipidus (DIR) is a rare X-linked hereditary disorder in which the renal collecting duct is unresponsive to arginine vasopressin; thus, the urine is consistently hypotonic to plasma. Recently, the association between the V2 receptor gene (AVPR2) and DIR has been proven. We have determined the gene sequence of four family members, from three generations, of a large North American family with CNDI who were originally part of the study used to formulate the Hopewell hypothesis. It had been proposed that a single DIR gene defect was introduced to North America by a member of an Ulster Scot kindred arriving on the ship Hopewell in 1761. DNA sequencing of the AVPR2 has identified a single base transversion from G-->A which changes tryptophan 71 to a stop codon in affected patients. This point mutation causes a truncation of the receptor leading to an essentially null allele. These data and other recently described mutations in the AVPR2 in North American pedigrees, descended from Ulster Scot ancestors and other origins, make the assertion of a founder effect proposed in the Hopewell hypothesis invalid.
authors.affiliation: Renal Unit, (Medical Services), Massachusetts General Hospital, Charlestown 02129.
authors.forename: E J
authors.initials: EJ
authors.lastname: Holtzman
authors.forename: L F
authors.initials: LF
authors.lastname: Kolakowski
authors.forename: D
authors.initials: D
authors.lastname: O'Brien
authors.forename: J D
authors.initials: JD
authors.lastname: Crawford
authors.forename: D A
authors.initials: DA
authors.lastname: Ausiello
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D015252:Deoxyribonucleases, Type II Site-Specific; D003919:Diabetes Insipidus / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006580:Genetic Carrier Screening; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017483:Receptors, Vasopressin / Q000235:genetics*; D015183:Restriction Mapping; D014960:X Chromosome
chemical_list: D017931:DNA Primers; D017483:Receptors, Vasopressin; C051612:endodeoxyribonuclease BanI; D015252:Deoxyribonucleases, Type II Site-Specific