Fetal anomalies
Gene: PIEZO1

PIEZO1 (piezo type mechanosensitive ion channel component 1)
EnsemblGeneIds (GRCh38): ENSG00000103335
EnsemblGeneIds (GRCh37): ENSG00000103335
OMIM: 611184, Gene2Phenotype
PIEZO1 is in 7 panels

2 reviews

Anna de Burca (Oxford University Hospitals NHS Foundation Trust)

Green List (high evidence)

PMID:26333996 reports biallelic variants in PIEZO1 in 6 unrelated individuals with lymphatic dysplasia; probands in 4 families presented with non-immune fetal hydrops. Variants were a combination of missense, splice variants and nonsense, consistent with a loss of function mechanism. PMID: 23695678 reports monoallelic variants in PIEZO1 in 11 probands with dehydrated hereditary stomatocytosis. The phenotype was variable and in some cases associated with perinatal oedema. Functional evidence supported a gain of function mechanism. Due to the variable phenotype and mode of pathogenicity of the monoallelic condition, I think it is appropriate to include PIEZO1 on this panel for loss of function, biallelic variants, associated with Lymphatic malformation 6 only.
Created: 2 Jan 2019, 7:48 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Lymphatic malformation 6; Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema

Publications

PMID: 26333996
23695678

Created: 2 Jan 2019, 7:48 a.m.

Panel version: 0.34

Rebecca Foulger (Genomics England curator)

I don't know

Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a case with two homozygous variants in PIEZO1 (one pathogenic, one VUS), where the main ultrasound finding was Hydrops (Table 1).
Created: 24 May 2019, 10:53 a.m.

Additional evidence from PAGE study: Diagnostic Compound heterozygous variants identified in PIEZO1 from fetalexome sequencing inLord et al., 2019 (PMID:30712880).
Created: 18 Apr 2019, 3:51 p.m.

This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene.
Created: 4 Apr 2019, 2:03 p.m.

Removed watchlist tag following clinical review by Anna de Burca.
Created: 7 Jan 2019, 11:25 a.m.

Comment on mode of inheritance: Anna's suggestion of biallelic MOI is based on Lymphatic malformation 6 phenotype (MIM:616843) which has AR inheritance and fetally-relevant phenotype. After further discussion we agreed to include AD inheritance for PIEZO1 based on reviews on the Fetal hydrops panel: in summary, PMID:26333996 (Fotiou et al., 2015) reports that NIHF variably occurs in DHS (with AD inheritance), and a review by Tessa Homfray lists both AD and AR inheritance.
Created: 7 Jan 2019, 11:24 a.m.

Comment on list classification: Updated rating from Amber to Green: Rated Green on relevant V1 panel(s) PLUS phenotype (hydrops) appropriate for fetal panel, as noted by Helen Brittain and Anna de Burca (Genomics England Clinical team).
Created: 18 Dec 2018, 9:58 p.m.

Comment on mode of inheritance: 'BOTH monoallelic and biallelic' MOI is recorded for PIEZO1 on the 'Fetal hydrops' panel. Althought the DDG2P MOI is 'biallelic' for Congenital lymphatic dysplasia with hydrops and/or lymphoedema, the monoallelic MOI comes from the additional gene list compiled by PAGE.
Created: 18 Dec 2018, 9:56 p.m.

In original PAGE file, PIEZO1 is listed as biallelic for Congenital lymphatic dysplasia with hydrops and/or lymphoedema, and both monoallelic and biallelic for phenotypes in the additional gene file.
Created: 18 Dec 2018, 9:53 p.m.

'watchlist' tag added to highlight different DD-G2P ratings for this gene.
Created: 8 Nov 2018, 8:58 p.m.

In the original PAGE file: rated as Probable for Congenital lymphatic dysplasia with hydrops and/or lymphoedema, and rated as Confirmed in the Additional gene list.
Created: 8 Nov 2018, 4:45 p.m.

Phenotypes
Hydrops

Publications

30712880

Created: 8 Nov 2018, 4:45 p.m.

Panel version: 0.273

Details

Mode of Inheritance

BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Sources

Expert Review Green
PAGE Additional Gene List
PAGE DD-Gene2Phenotype

Phenotypes

Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, OMIM:194380
Lymphatic malformation 6, OMIM:616843
Congenital lymphatic dysplasia with hydrops and/or lymphoedema

OMIM

611184

Clinvar variants

Variants in PIEZO1

Penetrance

None

Publications

Panels with this gene

History Filter Activity

8 Dec 2021, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: PIEZO1 were changed from hydrops fetalis gene 616843; Congenital lymphatic dysplasia with hydrops and/or lymphoedema to Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, OMIM:194380; Lymphatic malformation 6, OMIM:616843; Congenital lymphatic dysplasia with hydrops and/or lymphoedema

23 May 2019, Gel status: 3