Genetic Renal Diseases in Children

Title: Genetic Renal Diseases in Children
Author: Hildebrandt, Friedhelm
Publisher: Current Opinion in Pediatrics
Date Published: April 01, 1995
Reference Number: 70
In this review, a survey is given of genetic renal diseases in which recent progress has been made regarding the study of their molecular genetics. Diseases in which the responsible gene has been identified are discussed first, followed by a description of diseases in which successful chromosomal mapping has been achieved. The recent progress in this field will lead to advances in the diagnosis and understanding of the pathogenic mechanisms of genetic renal diseases and, potentially, will have implications for therapeutic interventions. The International Studies of Genetic Renal Diseases, which promotes the study of genetic renal disease, has recently provided an international database called kidbase, which is accessible via the Internet.

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)

Over the recent years, molecular biologists have developed and refined two different approaches to map or isolate genes responsible for genetic kidney disorders: functional cloning and positional cloning.

If researchers have s strong idea of what gene is responsible for a disorder caused by a single gene mutation, they can derive the amino acid sequence of the purified protein synthesized by the suspect gene. This is functional cloning. Once they have the amino acid sequence, it is possible to fully characterized the suspect gene and identify mutations within it.

In the absence of prior knowledge of a functional protein defect, the gene causing the disease is generally identified through positional cloning. This involves examining the chromosomes of individuals affected with the same disease in the hope that chromosomal aberrations the patients may hold in common will point to the location of the disease-causing gene.

In the case of nephrogenic diabetes insipidus (NDI), two genes have been identified that, when mutated, can cause the disorder: the vasopressin-2 (V2R) gene and the aquaporin-2 (AQP2) gene. People affected with inherited NDI either have a mutated V2R gene or a mutated AQP2 gene. Ninety percent of the cases result from a mutated V2R gene. The International Studies of Genetic Renal Diseases provides an international database called Kidbase in order to initiate or facilitate collaborative studies on genetic inherited renal diseases.