Inherited Diseases of the Kidney
| Title: | Inherited Diseases of the Kidney |
|---|---|
| Authors: | Germino, Gregory G.; Somlo, Stefan |
| Publisher: | Current Opinion in Nephrology and Hypertension |
| Date Published: | May 01, 1993 |
| Reference Number: | 135 |
It has long been known that a number of diseases affecting the kidney are the result of genetic defects passed on through the generations. Whereas some of these defects are rare, others, e.g., the cystic diseases, are among the most common. Our understanding of the underlying pathobiology in these disorders based on physiologic and cell biologic studies is variable--we suspect that the V2 vasopressin receptor is defective in nephrogenic diabetes insipidus; we know that the glomerular basement membrane in Alport syndrome is abnormal; we suspect that a tumor suppressor gene is defective in Wilms tumor; and we lack a unifying hypothesis regarding cystic degeneration of the kidney. The advent and rapid progress of molecular biology have permitted an entirely new approach to understanding these diseases, allowing the expected identification of mutations in the V2 receptor, the unexpected finding that a novel collagen gene is responsible for many Alport syndrome cases, and the somewhat less-unexpected finding that only one of several genes responsible for renal cancers has been identified. Further, we are beginning to unravel the complex pathways responsible for cystic changes in the kidney. This review integrates these molecular biologic discoveries with the known pathobiology of disease to achieve a more complete understanding of the whole process.
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)
The most common form of inherited NDI is X-linked recessive NDI. Genes come in pairs, one inherited from the mother and one from the father. Sometimes one or both of the gene pairs may be mutated and this could result in some type of dysfunction. Normally, if a gene is recessive, it must be inherited in a double dose - one from the father and one from the mother-- for it to be able to express itself physically. However, the gene responsible for NDI is located on the X chromosome and males have only one X chromosome (inherited from the mother), whereas females have two. So if the offspring is a male and he inherits the gene responsible for NDI from his mother, he is likely to express NDI because there is no corresponding gene from the father to mask the inherited gene's expression. In short, in X-linked recessive disorders, females carry the defective gene and males are more likely to express the dysfunction caused by the gene, in this case, NDI.
Researchers discovered the gene responsible for NDI was the vasopressin-2 (V2R) gene. V2R, when functional, binds with the antidiuretic hormone, arginine vasopressin (AVP). This initiates a molecular sequence that allows the kidney to concentrate urine, reabsorb water and thus balance body water. Researchers worldwide have discovered many different mutations in the V2R gene, many of which have resulted in NDI. The authors state that as researchers study the mutations, it will give insight into the relation between the structure of the V2R gene and its function.