PKHD1 biallelic defects caused Severe Hepatic Fibrosis and polycystic kidney: Identification of a novel pathogenic variant in a Chinese family

Background: Autosomal recessive polycystic kidney disease (ARPKD) is a rare hereditary ciliopathy, clinically characterized by fibrocystic changes in the kidneys and liver. The disease is manifested by hepatic fibrosis and significantly enlarged, echogenic kidneys with fusiform dilation of the collecting ducts. ARPKD is predominantly associated with homozygous or compound heterozygous mutations in the PKHD1 gene, which encodes the protein fibrocystin.

Clinical case: In this study, we report a case involving a young Chinese female who presented with recurrent upper gastrointestinal bleeding, abdominal distension, and hepatosplenomegaly. Imaging studies revealed portal hypertension and bilateral renal involvement, while a liver biopsy indicated portal fibrosis with ductal plate malformation. Genetic analysis identified her as a compound heterozygote for a known pathogenic variant, c.2107G>A (p.D703N), and a novel variant, c.4820A>G (p.Y1607C), in the PKHD1 gene.

Conclusion: Family-based studies have shown that individuals carrying the novel variant exhibit a hepatic abnormal phenotype. Bioinformatics analysis suggests that this novel mutation may impact the protein structure by altering hydrogen bond interactions with other amino acids.

Keywords: PKHD1, autosomal recessive polycystic kidney disease (ARPKD), a novel pathogenic variant, hepatic fibrosis, mutation spectrum.