Dilated Cardiomyopathy and conduction defects

Gene: PPP1R13L

Green List (high evidence)

PPP1R13L (protein phosphatase 1 regulatory subunit 13 like)
EnsemblGeneIds (GRCh38): ENSG00000104881
EnsemblGeneIds (GRCh37): ENSG00000104881
OMIM: 607463, Gene2Phenotype
PPP1R13L is in 3 panels

5 reviews

Rebecca Whittington (South West GLH)

Red List (low evidence)

No phenotype on OMIM
Created: 25 Mar 2019, 4:30 p.m.
Mouse model showed progressive DCM (Herron 2005 Hum Mol Genet. 2005 Mar 1;14(5):667-77). HGMD: 2017 paper: Falik-Zaccai (2017) EMBO Mol Med 9, 319 - reported five Arab Christian infants, aged 430 months from four families, were diagnosed with DCM associated with mild skin, teeth, and hair abnormalities. All passed away before age 3 and were homozygous for the same nonsense variant in this gene. Patients fibroblasts and PPP1R13L-knocked down human fibroblasts presented higher expression levels of pro-inflammatory cytokine genes in response to lipopolysaccharide, as well as Ppp1r13l-knocked down murine cardiomyocytes and hearts of Ppp1r13l-deficient mice.
Created: 25 Mar 2019, 4:27 p.m.
Paediatric onset only - paediatric panel
Created: 25 Mar 2019, 4:24 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Red List (low evidence)

Not fully reviewed however doesn't appear to be associated with primary non-syndromic teen/adult onset DCM.
Created: 17 Jan 2019, 5:41 p.m.

Louise Daugherty (Genomics England Curator)

Comment on list classification: Changed from Red to Green. Appropriate phenotypes, sufficient cases, and external review comment denoting extra cases and evidences all support gene-disease association.
Created: 19 Nov 2018, 4:57 p.m.
Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green
Created: 19 Nov 2018, 4:39 p.m.

Sian Ellard (University of Exeter Medical School)

Green List (high evidence)

In addition to the one published family (with 5 affected individuals), we are aware of 4 additional cases from 3 families found through GeneMatcher after a gene-agnostic trio analysis highlighted this gene in a family participating in the 100,000 Genomes Project. All the additional cases had dilated cardiomyopathy and either underwent heart transplantation or died before the age of 10 years.
Created: 13 Nov 2018, 7:39 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Variants in this GENE are reported as part of current diagnostic practice

Ellen McDonagh (Genomics England Curator)

PMID: 28069640 describes a large extended family pedigree, with 5 affected infants with Dilated cardiomyopathy who all died before the age of 3. A SNP predicted to cause a premature termination codon was identified c.2241C > G, p.Tyr747Ter in 3 affected patients as homozygous status and heterozygous in the patients. Sequencing was unavailable for two affected sisters. There is also evidence in animals - deficient mice die suddenly of cardiac death (PMID: 25691752), and in 13 Poll Hereford cattle with Cardiomyopathy and woolly haircoat syndrome (a lethal autosomal recessive disorder) a frameshift variant was identified, predicted to cause a premature stop codon. This gene is not currently associated with a disease in OMIM or Gene2Phenotype.
Sources: Literature
Created: 5 Nov 2018, 10:29 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
cardio-cutaneous syndrome; sudden cardiac death

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • South West GLH
  • Wessex and West Midlands GLH
  • Expert Review Green
  • Literature
Phenotypes
  • cardio-cutaneous syndrome
  • sudden cardiac death
OMIM
607463
Clinvar variants
Variants in PPP1R13L
Penetrance
None
Publications
Panels with this gene

History Filter Activity

21 Feb 2019, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to PPP1R13L.

17 Jan 2019, Gel status: 3

Added New Source, Status Update

Ellen McDonagh (Genomics England Curator)

Source Wessex and West Midlands GLH was added to PPP1R13L. Rating Changed from Green List (high evidence) to Green List (high evidence)

19 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: ppp1r13l has been classified as Green List (High Evidence).

19 Nov 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: PPP1R13L were set to 28069640; 25691752; 19016676

5 Nov 2018, Gel status: 1

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

Ellen McDonagh (Genomics England Curator)

gene: PPP1R13L was added gene: PPP1R13L was added to Dilated Cardiomyopathy and conduction defects. Sources: Literature Mode of inheritance for gene: PPP1R13L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPP1R13L were set to 28069640; 25691752; 19016676 Phenotypes for gene: PPP1R13L were set to cardio-cutaneous syndrome; sudden cardiac death