Association of a novel PKHD1 mutation in a family with autosomal dominant polycystic liver disease

Background: Autosomal dominant polycystic liver disease (ADPLD) is characterized by multiple cysts in the liver without (or only occasional) renal cysts. At least seven genes are associated with high risk for developing ADPLD; however, clear genetic involvement is undetermined in more than 50% of ADPLD patients. Methods: To identify additional ADPLD-associated genes, we collected 18 unrelated Chinese ADPLD cases, and performed whole exome sequencing on all the participants. After filtering the sequencing data against the human gene mutation database (HGMD) professional edition, we identified new mutations. We then sequenced this gene in family members of the patient. Results: Among the 18 ADPLD cases analyzed by whole exome sequencing, we found 2 cases with a PRKCSH mutation (similar to 11.1%), 2 cases with a PKD2 mutation (similar to 11.1%), 1 case with both PKHD1 and PKD1 mutations (similar to 5.6%), 1 case with GANAB mutation (similar to 5.6%), 1 case with PKHD1 mutation (similar to 5.6%), and 1 case with PKD1 mutations (similar to 5.6%). We identified a new PKHD1 missense mutation in an ADPLD family, in which both patients showed innumerable small hepatic cysts, as reported previously. Additionally, we found that PRKCSH and SEC63 mutation frequencies were lower in the Chinese population compared with those in European and American populations. Conclusions: We report a family with ADPLD associated with a novel PKHD1 mutation (G1210R). The genetic profile of ADPLD in the Chinese population is different from that in European and American populations, suggesting that further genetic research on genetic mutation of ADPLD in the Chinese population is warranted.