Dg. Bichet et al., X-LINKED NEPHROGENIC DIABETES-INSIPIDUS MUTATIONS IN NORTH-AMERICA AND THE HOPEWELL HYPOTHESIS, The Journal of clinical investigation, 92(3), 1993, pp. 1262-1268
In X-linked nephrogenic diabetes insipidus (NDI) the urine of male pat
ients 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 a
nd Crawford suggested that most NDI patients in North America shared c
ommon ancestors of Ulster Scot immigrants who arrived in Halifax in 17
61 on the ship Hopewell. A link between this family and a large Utah k
indred was also suggested. DNA was obtained from 17 affected male pati
ents from the ''Hopewell'' kindred and from four additional families f
rom Nova Scotia and New Brunswick who shared the same Xq28 NDI haploty
pe. The Utah kindred and two families (Q2, Q3) from Quebec were also s
tudied. 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-link
ed NDI for the largest number of related male patients living in North
America. Other families (Utah, Q2 and Q3) that are historically and e
thnically unrelated bear other mutations in the V2 receptor gene.