A Null Mutation in the Vasopressin V2 Receptor Gene (AVPR2) Associated with Nephrogenic Diabetes Insipidus in the Hopewell Kindred
|Title:||A Null Mutation in the Vasopressin V2 Receptor Gene (AVPR2) Associated with Nephrogenic Diabetes Insipidus in the Hopewell Kindred|
|Authors:||Holtzman, M.D., Eliezer J.; Kolakowski, PhD, Lee F.; O'Brien, David; Crawford, M.D., John D.; Ausiello, M.D., Dennis A.|
|Publisher:||Human Molecular Genetics|
|Date Published:||August 01, 1993|
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
In 1969, Bode and Crawford proposed that most North American NDI patients were descendants of a common ancestral line, a group of Ulster Scots who arrived in Canada in 1761 aboard the ship, Hopewell. More recently, the association between mutations in the vasopressin-2 receptor (V2R) gene and NDI have been established. Holtzman, et al., analyzed the V2R gene mutations of one family lineage directly connected to the original Ulster Scot clan. The researchers found a distinct V2R mutation. This mutation involved a change in one of the nucleotide bases in the genetic sequence from a guanine to an adenine. This replacement results in a signal telling the mutated V2R gene to stop producing its V2R instead of telling it to produce a tryptophan amino acid. This caused the gene to produce a very premature truncation of the V2R, leaving it only 70 amino acids long instead of 371 amino acids long. This produced a V2R incapable of carrying out its required functions.
The researchers' data, combined with other research that shows that other V2R mutations have been found in descendants of the original Scots (as well as people from other ethnic origins) disproves Bode and Crawford's Hopewell hypothesis.