Intrafamilial Phenotype Variability in Nephrogenic Diabetes Insipidus
|Title:||Intrafamilial Phenotype Variability in Nephrogenic Diabetes Insipidus|
|Authors:||Kalenga, Karine; Persu, Alexandre; Goffin, Eric; Lavenne-Pardonge, Edith; van Cangh, Paul J.; Bichet, Daniel G.; Devuyst, Oliver|
|Publisher:||American Journal of Kidney Diseases|
|Date Published:||April 01, 2002|
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)
Kalenga, et al., studied a Belgian NDI family which was unusual in the respect that though two of the male siblings had the same V2R gene mutation, the older, a 45-year-old, had severe NDI symptoms and the younger, a 33-year-old, had mild ones. (The mother carried the same mutation, but was symptom free, as most female carriers are.) The older brother was mentally retarded, probably due to periods of dehydration in infancy as a result of NDI. He could not obtain stable employment and had an unsatisfactory social life. The younger brother had stable employment and a normal social life. During a water deprivation test, the older brother still could not concentrate urine, and injections of synthetic vasopressin (DDAVP) did not decrease his urinary output, whereas the younger brother was able to increase the concentration of his urine and did decrease his urinary output after DDAVP.
Their mutations (called R137H because it results in a histidine amino acid residue being in the position where an arginine residue should be) causes affected vasopressin-2 receptor proteins to be unable to reach the cell surface, where they must be to fulfill their function. It also reduces the V2R protein's ability to stimulate a major portion of the molecular sequence that leads to the kidney's ability to concentrate urine.
The R137H mutation has consistently been associated with severe NDI symptoms in people expressing the mutations. The researchers suggest that the milder symptoms of the younger brother could be due either to some modifying circumstances in the younger brother's V2R gene or variants in other genes involved in the urine-concentrating pathway. They also suggest that the consequences of NDI can be mitigated by early diagnosis along with proper treatment and pertinent information, and perhaps this accounted for the different outcomes in the brothers.