Study of Genotype and Phenotype Expression in Congenital Nephrogenic Diabetes Insipidus

Diabetes Insipidus, Nephrogenic

diabetes insipidus, endocrine disorders, rare disease

OBJECTIVES: I. Determine the relationship between genotype variations and clinical phenotype in patients with congenital nephrogenic diabetes insipidus.

PROTOCOL OUTLINE: A detailed family history is obtained from all participants. Whenever possible, standard growth curves of affected children are obtained. Participants then undergo clinical studies of antidiuretic function. A standard fluid deprivation-vasopressin challenge is performed with timed measurements of osmolality, electrolytes, creatinine, and vasopressin. The next day, blood pressure, plasma cyclic AMP, GMP, von Willebrand Factor, Factor VIII, and urine osmolality are measured during a water load desamino-D-arginine vasopressin (dDAVP) infusion test. Participants with a confirmed diagnosis of congenital diabetes insipidus are then treated with chlorothiazide. Daily urine volume and osmolality are determined before and after therapy. Sodium and fluid are not restricted. For each family, the entire vasopressin V2 gene of at least 1 affected male, and where possible at least 1 obligate carrier and 1 unaffected brother of a patient is sequenced. In addition, a detailed Xq28 haplotype analysis is done to identify the origin of de novo mutations. If no mutation is found and the disorder is not transmitted in an X-linked mode, both alleles of the gene that codes for aquaporin-II are also sequenced. DNA is collected by mail from as many kindred as possible who do not participate in the clinical studies.

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