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X-linked nephrogenic diabetes insipidus mutations in North America and the Hopewell hypothesis

Item Type:Article
Title:X-linked nephrogenic diabetes insipidus mutations in North America and the Hopewell hypothesis
Creators Name:Bichet, D.G. and Arthus, M.F. and Lonergan, M. and Hendy, G.N. and Paradis, A.J. and Fujiwara, T.M. and Morgan, K. and Gregory, M.C. and Rosenthal, W. and Didwania, A.
Abstract:In X-linked nephrogenic diabetes insipidus (NDI) the urine of male patients is not concentrated after the administration of the antidiuretic hormone arginine-vasopressin. This disease is due to mutations in the V2 receptor gene that maps to chromosome region Xq28. In 1969, Bode and Crawford suggested that most NDI patients in North America shared common ancestors of Ulster Scot immigrants who arrived in Halifax in 1761 on the ship Hopewell. A link between this family and a large Utah kindred was also suggested. DNA was obtained from 17 affected male patients from the "Hopewell" kindred and from four additional families from Nova Scotia and New Brunswick who shared the same Xq28 NDI haplotype. The Utah kindred and two families (Q2, Q3) from Quebec were also studied. The "Hopewell" mutation, W71X, is a single base substitution (G-->A) that changes codon 71 from TGG (tryptophan) to TGA (stop). The W71X mutation was found in affected members of the Hopewell and of the four satellite families. The W71X mutation is the cause of X-linked NDI for the largest number of related male patients living in North America. Other families (Utah, Q2 and Q3) that are historically and ethnically unrelated bear other mutations in the V2 receptor gene.
Keywords:Amino Acid Sequence, Base Sequence, Diabetes Insipidus, Genes, Haplotypes, Molecular Sequence Data, Oligodeoxyribonucleotides, Pedigree, Point Mutation, Restriction Fragment Length Polymorphism, Vasopressin Receptors, X Chromosome
Source:Journal of Clinical Investigation
Publisher:American Society for Clinical Investigation
Page Range:1262-1268
Date:September 1993
Official Publication:https://doi.org/10.1172/JCI116698
PubMed:View item in PubMed

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