IDENTIFICATION OF A LOCUS FOR PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS PFIC2 ON CHROMOSOME 2Q24

Progressive familial intrahepatic cholestasis (PFIC; OMIM 211600) is t he second most common familial cholestatic syndrome presenting in infa ncy. A locus has previously been mapped to chromosome 18q21-22 in the original Byler pedigree, This chromosomal region also harbors the locu s for benign recurrent intrahepatic cholestasis (BRIC) a related pheno type. Linkage analysis in six consanguineous PFIC pedigrees from the M iddle East has previously excluded linkage to chromosome 18q21-22, ind icating the existence of locus heterogeneity within the PFIC phenotype , By use of homozygosity mapping and a genome scan in these pedigrees, a locus designated ''PFIC2'' has been mapped to chromosome 2q24. A ma ximum LOD score of 8.5 was obtained in the interval between marker loc i D2S306 and D25124, with all families linked.