Molecular Genetics Of Pathogenesis Of Congenital Nephrogenic Diabetes Insipidus

To maintain water and osmolyte balance, the mammalian kidney forms 180 litres of pro-urine per day, of this volume, nearly all water is reabsorbed. If the course is disturbed, organism will present morbidity. Nephrogenic diabetes insipidus (NDI) is a rare disease characterized by the inability of the kidney to concentrate urine. Polyuria and polydipsia are present at birth, and need to be recognized early to avoid repeated episodes of dehydration that can result in mental retardation. The concentration defect is demonstrable within a few days of birth.NDI may be acquired or congenital. The acquired form of NDI is much more common than the congenital form, is almost always less severe. Our research is focus on congenital nephrogenic diabetes insipidus. About 90% of patients with congenital nephrogenic diabetes insipidus are males with the X-linked recessive form of the disease who have mutations in the arginine vasopressin receptor 2 gene (AVPR2), which codes for the vasopressin V2 receptor. In <10% of the families studied, congenital nephrogenic diabetes insipidus has an autosomal-recessive or autosomal-dominant mode of inheritance. Mutations have been identified in the aquaporin-2 gene (AQP2), which codes for the vasopressin-sensitive water channel. The functionally characterized mutants show a loss of function due to defects in their synthesis, processing, intracellular transport and in urine concentration.This article is based on the molecule genetics study on AQP2 and AVPR2 gene of several Chinese NDI patients. We isolated high-molecular-weight genomic DNA from peripheral blood leukocytes of NDI patients, and PCR amplified all exons of AQP2 and AVPR2 followed by direct sequencing, the result is compared with GenBank to identify the mutation. We found several significant mutations in 3 families with NDI. 3 mutations ( S167L, L309L, and a substitution in 3' untranslated region ) have been found in NDI patients in other countries. We think S167L isrelated with pathogeny. We also find a novel mutation in the intron of AQP2 (433 G>A), further research is required to find out the relationship between this mutation and NDI.Our work can contribute to the information of molecule genetics character of Chinese NDI patients and global scale study.