BENIGN RECURRENT INTRAHEPATIC CHOLESTASIS (BRIC) - EVIDENCE OF GENETIC-HETEROGENEITY AND DELIMITATION OF THE BRIC LOCUS TO A 7-CM INTERVAL BETWEEN D18S69 AND D18S64

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal reces sive liver disease characterized by multiple episodes of cholestasis w ithout progression to chronic liver disease. The gene was previously a ssigned to chromosome 18q21, using a shared segment analysis in three families from the Netherlands. Ln the present study we report the link age analysis of an expanded sample of 14 BRIC families, using 15 micro satellite markers from the 18q21 region, Obligate recombinants in two families place the gene in a 7-cM interval, between markers D18S69 and D18S64. All intervening markers had significant LOD scores in two-poi nt linkage analysis. Moreover, we identified one family in which the B RIC gene seems to be unlinked to the 18q21 legion, or that represents incomplete penetrance of the BRIC genotype.