title: Congenital hepatic fibrosis and portal hypertension in autosomal dominant polycystic kidney disease.
abstract: OBJECTIVE
  Autosomal dominant (ADPKD) and recessive (ARPKD) polycystic kidney diseases are the most common hepatorenal fibrocystic diseases (ciliopathies). Characteristics of liver disease of these disorders are quite different. All of the patients with ARPKD have congenital hepatic fibrosis (CHF) often complicated by portal hypertension. In contrast, typical liver involvement in ADPKD is polycystic liver disease, although rare atypical cases with CHF are reported. Our goal was to describe the characteristics of CHF in ADPKD.
  
  
  METHODS
  As a part of an intramural study of the National Institutes of Health on ciliopathies (www.clinicaltrials.gov, trial NCT00068224), we evaluated 8 patients from 3 ADPKD families with CHF. We present their clinical, biochemical, imaging, and PKD1 and PKHD1 sequencing results. In addition, we tabulate the characteristics of 15 previously reported patients with ADPKD-CHF from 11 families.
  
  
  RESULTS
  In all of the 19 patients with ADPKD-CHF (9 boys, 10 girls), portal hypertension was the main manifestation of CHF; hepatocelllular function was preserved and liver enzymes were largely normal. In all of the 14 families, CHF was not inherited vertically, that is the parents of the index cases had PKD but did not have CHF-suggesting modifier gene(s). Our 3 families had pathogenic mutations in PKD1; sequencing of the PKHD1 gene as a potential modifier did not reveal any mutations.
  
  
  CONCLUSIONS
  Characteristics of CHF in ADPKD are similar to CHF in ARPKD. ADPKD-CHF is caused by PKD1 mutations, with probable contribution from modifying gene(s). Given that both boys and girls are affected, these modifier(s) are likely located on autosomal chromosome(s) and less likely X-linked.
authors.affiliation: Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: O'Brien
authors.forename: Esperanza
authors.initials: E
authors.lastname: Font-Montgomery
authors.forename: Linda
authors.initials: L
authors.lastname: Lukose
authors.forename: Joy
authors.initials: J
authors.lastname: Bryant
authors.forename: Katie
authors.initials: K
authors.lastname: Piwnica-Worms
authors.forename: Hailey
authors.initials: H
authors.lastname: Edwards
authors.forename: Lauren
authors.initials: L
authors.lastname: Riney
authors.forename: Angelica
authors.initials: A
authors.lastname: Garcia
authors.forename: Kailash
authors.initials: K
authors.lastname: Daryanani
authors.forename: Peter
authors.initials: P
authors.lastname: Choyke
authors.forename: Parvathi
authors.initials: P
authors.lastname: Mohan
authors.forename: Theo
authors.initials: T
authors.lastname: Heller
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.forename: Meral
authors.initials: M
authors.lastname: Gunay-Aygun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002875:Chromosomes; D005260:Female; D060045:Genes, Modifier; D006801:Humans; D006975:Hypertension, Portal / Q000209:etiology*; D008099:Liver / Q000201:enzymology / Q000473:pathology* / Q000502:physiology; D008103:Liver Cirrhosis / Q000151:congenital / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications* / Q000235:genetics / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics; D050396:TRPP Cation Channels / Q000235:genetics*; D055815:Young Adult
chemical_list: D011956:Receptors, Cell Surface; D050396:TRPP Cation Channels; C451750:PKHD1 protein, human