Lipodystrophy - childhood onset

Gene: PLIN1

Green List (high evidence)

PLIN1 (perilipin 1)
EnsemblGeneIds (GRCh38): ENSG00000166819
EnsemblGeneIds (GRCh37): ENSG00000166819
OMIM: 170290, Gene2Phenotype
PLIN1 is in 5 panels

6 reviews

Anna de Burca (Genomics England Curator)

Green List (high evidence)

As discussed with NHS endocrine specialist test group on 28.01.19, haploinsufficiency for this gene is NOT a cause of lipodystrophy, see PMID:30020498. As Robert Semple noted in 2015, all pathogenic mutations to date are frameshifts leading to translation of an aberrent C terminus of the protein ie. a dominant negative mechanism. Therefore, this gene is appropriate for inclusion on this panel, but only frameshift variants should be reported, as loss of function variants would not be expected to cause disease.
Created: 5 Mar 2019, 1:06 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Lipodystrophy, familial partial, type 4

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Louise Daugherty (Genomics England Curator)

Comment on list classification: This gene was downgraded from Green to Amber due to the findings of PMID: 30020498 - variants in this gene predicted to cause haplosufficiency are not a cause of familial partial lipodystrophy.
Created: 20 Dec 2018, 5:46 p.m.

Ellen McDonagh (Genomics England Curator)

Comment on list classification: This gene was downgraded from Green to Amber due to the findings of PMID: 30020498 - variants in this gene predicted to cause haplosufficiency are not a cause of familial partial lipodystrophy.
Created: 20 Dec 2018, 10:51 a.m.

David Savage (IMS MRL, Uni. Cambridge)

Green List (high evidence)

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Associated with phenotype in OMIM, not in G2P. At least three frame-shifting variants reported in five unrelated families
Created: 12 Aug 2016, 3:35 p.m.

Robert Semple (University of Cambridge)

Green List (high evidence)

All pathogenic mutations to date are frameshifts leading to translation of an aberrent C terminus of the protein
Created: 12 Oct 2015, 8:43 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Familial Partial Lipodystrophy

Publications

Mode of pathogenicity
Other

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Lipodystrophy, familial partial, type 4, 613877
OMIM
170290
Clinvar variants
Variants in PLIN1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

16 Apr 2019, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: PLIN1 were set to 21345103; 25114292; 30020498

5 Mar 2019, Gel status: 3

Entity classified by Genomics England curator

Anna de Burca (Genomics England Curator)

Gene: plin1 has been classified as Green List (High Evidence).

8 Jan 2019, Gel status: 2

Panel promoted to version 1.0

Ellen McDonagh (Genomics England Curator)

Robert Semple: All pathogenic mutations to da

4 Jan 2019, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: plin1 has been classified as Amber List (Moderate Evidence).

20 Dec 2018, Gel status: 2

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: plin1 has been classified as Amber List (Moderate Evidence).

20 Dec 2018, Gel status: 4

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene: PLIN1 were set to 21345103; 25114292

19 Dec 2018, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Sarah Leigh (Genomics England Curator)

gene: PLIN1 was added gene: PLIN1 was added to Lipodystrophy - childhood onset. Sources: Radboud University Medical Center, Nijmegen,Expert Review Green Mode of inheritance for gene: PLIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PLIN1 were set to 21345103; 25114292 Phenotypes for gene: PLIN1 were set to Lipodystrophy, familial partial, type 4, 613877