PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS (PFIC) - EVIDENCE FOR GENETIC-HETEROGENEITY BY EXCLUSION OF LINKAGE TO CHROMOSOME 18Q21-Q22

Progressive familial intrahepatic cholestasis (PFIC) is the second mos t common form of familial intrahepatic cholestasis. The genes for PFIC and for a milder form of the disease, benign recurrent intrahepatic c holestasis (BRIC), were recently mapped to a 19-cM region on chromosom e 18q21-q22. The results suggest that PRC and BRIC are allelic disease s. We have studied 11 Swedish patients from eight families with clinic al and biochemical features consistent with PFIC. The families were ge notyped for markers D18S69, D18S64, D18S55 and D18S68, spanning the PF IC candidate region. Unexpectedly, the segregation of haplotypes exclu ded the entire region in three families, and no indications for shared haplotypes were found in the patients of the six remaining families. A four-point linkage analysis of all families excluded linkage from D1 8S69 to D18S55 (Z(max) < -5). Thus, our data strongly suggest the pres ence of a second, yet unknown, locus for PRC. The results indicate tha t great care should be taken when using 18q markers for prenatal diagn osis and genetic counseling for the disease.