Neonatal cholestasis

Gene: POLG

Green List (high evidence)

POLG (DNA polymerase gamma, catalytic subunit)
EnsemblGeneIds (GRCh38): ENSG00000140521
EnsemblGeneIds (GRCh37): ENSG00000140521
OMIM: 174763, Gene2Phenotype
POLG is in 31 panels

4 reviews

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 6 variants reported in Mitochondrial DNA depletion syndrome 4A (Alpers type) 203700.
Created: 14 Aug 2018, 9:20 a.m.
Comment on list classification: Based on rating by clinical fellow Helen Brittain (Genomics England Curator).
Created: 14 Aug 2018, 9:17 a.m.

Helen Brittain (Genomics England Curator)

Green List (high evidence)

Neonatal hepatic dysfunction is a feature of Mitochondrial DNA depletion syndrome 4A (Alpers type). This is therefore within the anticipated scope of the panel, and genes causing related presentations are rated green (MPV17 & DGUOK). It does however present with severe neurological manifestations in addition e.g. neurodevelopmental delay / seizures. If the panel is refined with the aim of fulfilling a more focal / isolated hepatic presentation in infancy then this gene would need to be re-considered.
Created: 27 Jul 2018, 1:39 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial DNA depletion syndrome 4A (Alpers type) 203700

Ellen McDonagh (Genomics England Curator)

PMID: 20142534 - reported variability in features reported in 4 cases (two sets of sblings) of Alpers-like hepatocerebral syndrome who were compound heterozygous (all sharing one of the same variants) - one boy displayed cholestasis. All patients had liver disease. In OMIM, Mitochondrial DNA depletion syndrome 4A (Alpers type) has the features Liver failure, Abnormal bile duct architecture and Bile duct proliferation. I am unsure whether this gene should be Green on this panel. This is Green on the Mitochondrial disorders Version 1.66, Neonatal and familial gastrointestinal neuromuscular disorders Version 1.7, Undiagnosed metabolic disorders Version 1.77 panels. A literature search did not reveal any further cases linked to cholestasis.
Created: 25 Jul 2018, 1:33 p.m.

Jane Hartley (Birmingham Women and Children's Hospital)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
mitochondrial disease; cholestasis; liver failure

History Filter Activity

3 Sep 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

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

14 Aug 2018, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: polg has been classified as Green List (High Evidence).

14 Aug 2018, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4A (Alpers type) 203700

14 Aug 2018, Gel status: 3

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

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

14 Aug 2018, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: polg has been classified as Green List (High Evidence).

25 Jul 2018, Gel status: 2

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4A (Alpers type)

25 Jul 2018, Gel status: 2

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

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

25 Jul 2018, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene: POLG were set to 20142534

21 Jun 2018, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

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

18 May 2018, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

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

18 May 2018, Gel status: 1

Created

Ellen McDonagh (Genomics England Curator)

POLG was created by Ellen McDonagh