Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease in this country. It effects 50,000 people and costs in excess of $200 million per year for treatment of ESRD alone. Thus, its is important to expand our understanding of this disease. Our large and well- studied ADPKD population includes 314 families, one of whom is known to be ADPKD2 (chromosome 4). 521 adults with ADPKD, 100 children with ADPKD, and 109 unaffected children (defined by ultrasonography) have participated in the study since 1985. The project's specific aims reflect information gathered by us and others and utilize the recent cloning of the ADPKD gene (chromosome 16) and the identification of the locations of the ADPKD2 gene and the ARPKD gene. There are three specific aims. First, we will attempt to elucidate the relationship between phenotypic and genotypic variability by focusing on spontaneous mutations, children with very early onset disease, the phenotypic differences between ADKD1 and ADPKD2 subjects, the interfamily variability displayed by families at extremes of the clinical spectrum and the intrafamily variability displayed by sib-pairs who differ in their clinical expressions.
The second aim i s to further our understanding of ADPKD in children by identifying prognostic phenotypic characteristics in the children and in their parents and by conducting a pilot study on the effect of antihypertensive therapy on the progression of renal structural disease in ADPKD children. Thirdly, we will explore the natural history and genotype of ADPKD subjects with intracranial aneurysm by focusing on rescreening subjects both with and without intracranial aneurysms and on the genotype of families with multiple ADPKD subjects with intracranial aneurysms and individuals with recurrent intracranial aneurysms.
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