The purpose of this study is to test the hypothesis that searching for shared segments of genes by the use of gene mapping will distinguish subgroups of Byler syndrome/PFIC into molecular defined categories. This eventually may permit distinction among subgroups of Byler syndrome/PFIC on the basis of morphologic or clinical laboratory findings, as well as molecular work. The results of this study is expected to enhance our understanding of cholestasis as well as to improve the assessment of prognosis and the assignment of appropriate therapy via identification of gene defects and gene products which correspond to particular steps in bile secretion. Molecular biologic techniques will be used to analyze peripheral blood from patients and parents with Byler syndrome. If available, archival tissues will be used to extract genomic DNA, which will be analyzed for homozygosity at the BD locus, using microsatellite markers. The molecular biologic observations will be correlated with findings on light microscopy and TEM of the liver, as well as with clinical and biochemical data. It is hoped that insight into cholestasis will be gained by this work, with the eventual goal of developing effective therapies.
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