Identification of a locus for autosomal dominant polycystic liver disease,on chromosome 19p13.2-13.1

Polycystic liver disease (PCLD) is characterized by the growth of fluid-fil led cysts of biliary epithelial origin in the liver. Although the disease i s often asymptomatic, it can, when severe, lead to complications requiring surgical therapy. PCLD is most often associated with autosomal dominant pol ycystic kidney disease (ADPKD); however, families with an isolated polycyst ic liver phenotype without kidney involvement have been described. The clin ical presentation and histological features of polycystic liver disease in the presence or absence of ADPKD are indistinguishable, raising the possibi lity that the pathogenetic mechanisms in the diseases are interrelated. We ascertained two large families with polycystic liver disease without kidney cysts and performed a genomewide scan for genetic linkage. A causative gen e, PCLD, was mapped to chromosome 19p13.2-13.1, with a maximum LOD score of 10.3. Haplotype analysis refined the PCLD interval to 12.5 cM flanked by D 13S586/D19S583 and D13S593/D19S579. The discovery of genetic linkage will f acilitate diagnosis and study of this underdiagnosed disease entity. Identi fication of PCLD will be instrumental to an understanding of the pathogenes is of cyst formation in the liver in isolated PCLD and in ADPKD.