MAPPING OF A LOCUS FOR PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS (BYLER DISEASE) TO 18Q21-Q22, THE BENIGN RECURRENT INTRAHEPATIC CHOLESTASIS REGION

A locus for progressive familial intrahepatic cholestasis (PFIC), also known as Byler disease, has been mapped to a 19 cM region of chromoso me 18 by a search for shared segments, using patients from the Amish k indred in which the disorder was originally described, A similar liver disease, benign recurrent intrahepatic cholestasis (BRIC), recently h as been mapped to the same region, suggesting that these two diseases are caused by mutations in the same gene, Although PFIC and BRIC are c linically distinct diseases, episodic attacks of jaundice and pruritus , with elevated concentrations of bile acid in serum, are seen in both disorders, In PFIC patients, these attacks result in progressive live r damage and death, The clinical and biochemical features of PFIC and BRIC are suggestive of a defect in primary bite acid secretion, The bi ology of bile secretion is of great interest because of its vital impo rtance in digestion of dietary fats as well as in secretion of xenobio tics and metabolic waste products, Cloning of the gene (or genes) resp onsible for PFIC and BRIC will likely provide important insights into this pathway.