Neonatal cholestasis

Gene: PKHD1

Amber List (moderate evidence)

PKHD1 (PKHD1, fibrocystin/polyductin)
EnsemblGeneIds (GRCh38): ENSG00000170927
EnsemblGeneIds (GRCh37): ENSG00000170927
OMIM: 606702, Gene2Phenotype
PKHD1 is in 17 panels

3 reviews

Helen Brittain (Genomics England Curator)

Comment when marking as ready: I would support an amber rating. This is based upon the evidence that the vast majority of infantile presentations, the age that this panel is targeted at, involve renal disease; enlarged or polycystic kidneys. I would expect these cases to present primarily via the cystic renal disease route. There is evidence within PMID 16523049 of an isolated hepatic presentation in some cases considered to have a likely pathogenic variant, namely; 1 year old with hepatomegaly and three people with cholangitis, however they were aged 25 / 37 / 40 years at presentation.

Amber and watchlist considered appropriate, whilst further evidence is gathered of isolated hepatic presentation in young infants.
Created: 27 Jul 2018, 11:32 a.m.

Ellen McDonagh (Genomics England Curator)

Comment on list classification: This gene has a high level of evidence for implication in polycystic kidney disease, which can eventually develop into cholestasis (PMID: 23593929); however, they are unlikely to present with cholestasis without renal failure or polycystic kidneys in which case other gene panels would be applied - this gene is Green on the Unexplained kidney failure in young people Version 1.13, Rare multisystem ciliopathy disorders Version 1.45, Cystic kidney disease Version 1.26. Therefore it is not clear that this gene should be Green on this panel.
Created: 25 Jul 2018, 1:08 p.m.

Jane Hartley (Birmingham Women and Children's Hospital)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
autosomal recessive polycystic kidney disease; cholestasis; portal hypertension; congenital hepatic fibrosis

History Filter Activity

3 Sep 2018, Gel status: 2

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

This panel has been subjected to extensive internal and external review.

27 Jul 2018, Gel status: 2

Entity classified by Genomics England curator

Helen Brittain (Genomics England Curator)

Gene: pkhd1 has been classified as Amber List (Moderate Evidence).

27 Jul 2018, Gel status: 2

Set Phenotypes

Helen Brittain (Genomics England Curator)

Phenotypes for gene: PKHD1 were set to Polycystic kidney disease 4, with or without hepatic disease 263200

27 Jul 2018, Gel status: 2

Set mode of inheritance

Helen Brittain (Genomics England Curator)

Mode of inheritance for gene: PKHD1 was changed from to BIALLELIC, autosomal or pseudoautosomal

25 Jul 2018, Gel status: 2

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: pkhd1 has been classified as Amber List (Moderate Evidence).

21 Jun 2018, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

Victorian Clinical Genetics Services was added to PKHD1. Panel: Cholestasis

18 May 2018, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

PKHD1 was added to Cholestasis panel. Sources: Emory Genetics Laboratory

18 May 2018, Gel status: 1

Created

Ellen McDonagh (Genomics England Curator)

PKHD1 was created by Ellen McDonagh