Characterization of an Aquaporin-2 Water Channel Gene Mutation Causing Partial Nephrogenic Diabetes Insipidus in a Mexican Family: Evidence of Increased Frequency of the Mutation in the Town of Origin
|Title:||Characterization of an Aquaporin-2 Water Channel Gene Mutation Causing Partial Nephrogenic Diabetes Insipidus in a Mexican Family: Evidence of Increased Frequency of the Mutation in the Town of Origin|
|Authors:||Boccalandro, Christina; de Mattia, Fabrizio; Guo, Dong-Chuan; Xue, Li; Orlander, Philip; King, Terri M.; Gupta, Prateek; Deen, Peter M.T.; Lavis, Victor R.; Milewicz, Dianna M.|
|Publisher:||Journal of American Society of Nephrology|
|Date Published:||May 01, 2004|
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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)
Boccalandro, et al., discovered a new AQP2 mutation: AQP2-V168M. This mutation is inherited in a recessive manner, which means both biological parents must have a mutant AQP2 gene. The research team was able to discover and describe how AQP2-V168M malfunctions and gives rise to NDI. They were also able to trace the source of the mutation to a small Mexican town.
AQP2-V168M results in a form of NDI that is not as severe in its effects as usual because AQP2-V168M is partially functional. That is, like most mutant AQP2, a large number of AQP2-V168M are retained in the ER. However, enough of the partially functional mutant is able to travel to the cell membrane to let water enter the cell. Normally, treatment with dDAVP, a synthetic analog of the hormone, arginine vasopressin (AVP) has no effect on NDI patients because NDI is not due to lack of AVP. However, the people with NDI due to AQP2-V168M did experience a reduction in the severity of their NDI symptoms. They experience reduced thirst and urine output and more concentrated urine.
Tracing the origin of this mutation back to a small Mexican town, the researchers found that 30% of the population carried the AQP2-V168M gene mutation on one of their chromosomes. Since a person must have the mutant gene on both chromosomes (inheriting the mutated gene from both mother and father) to express NDI, 1% of the town expressed NDI. However, since so many of the people of the town could pass the mutation on to their offspring, the researchers helped the local health care providers to have a deeper understanding of the problem.