Fetal hydrops

Gene: PIEZO1

Green List (high evidence)

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

3 reviews

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: Rated as green, and mode of inheritance complete.
Created: 19 Dec 2016, 11 a.m.
Comment on mode of inheritance: Listed MOI as suggested by Tessa Homfray: both monallelic and bilallelic. PIEZO1 is biallelic for LMPH3 (OMIM:616843) which presents with NIHF (non-immune hydrops fetalis). In addition, PIEZO1 is monoallelic for DHS (194380). Although this disorder isn't widely associated with Fetal hydrops, PMID:26333996 (Fotiou et al., 2015) says that NIHF variably occurs in DHS.
Created: 19 Dec 2016, 11 a.m.
Comment on list classification: Updated rating from Red to Green: 2 expert reviews for PIEZO1 are both green and >3 cases in OMIM of PIEZO1 mutations in Lymphedema, hereditary, III (LMPH3, OMIM:616843), a disorder with a high incidence of non-immune fetal hydrops (NIHF).
Created: 15 Dec 2016, 2:29 p.m.
Hereditary lymphedema III (LMPH3, OMIM:616843) is a form of generalized lymphatic dysplasia (GLD), with a high incidence of nonimmune hydrops fetalis (NIHF). >3 PIEZO1 variants are recorded in OMIM for LMPH3 (4 from PMID:26333996/Fotiou et al., 2015).
Created: 15 Dec 2016, 2:26 p.m.
PMID:26387913 (Lukacs et al., 2015) describe a family with a pair of sibs affected with a congenital lymphatic dysplasia. II.1 presented at birth with hydrops and bilateral chylothorax, Both affected sibs were compound heterozygotes for a PIEZO1 splicing variant, c.3455+1G>A and a missense variant, c.6085G>C;p.Gly2029Arg.
Created: 15 Dec 2016, 2:22 p.m.
PMID:26333996 (Fotiou et al., 2015) identified 2 sibling pairs and 1 sporadic case of GLD with mutations in the PIEZO1 gene. Nonimmune hydrops fetalis (NIHF) was documented in 2 of the families, with in-utero death of 1 sibling. Fotiou et al., identified 5 additional patients from 3 similarly affected families with a PIEZO1 mutation. Of the 10 patients, 7 had NIHF and 2 died in utero.
Created: 15 Dec 2016, 2:18 p.m.
PIEZO1 is included in the gene panel for Fetal hydrops based on the perinatal edema phenotype associated with PIEZO1 by Radboud.
Created: 10 Oct 2016, 9:55 a.m.

Tessa Homfray (Consultant Medical Genetics NHS)

Green List (high evidence)

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
2nd trimester fetal hydrops, Nuchal translucency likely to be normal. Lethal and non lethal cases within the same family

Diana Wellesley (nhs)

Green List (high evidence)

Well established association with hydrops
Created: 22 Nov 2016, 11:42 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hereditary lymphoedema type III OMIM 616843

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Lymphedema, hereditary, III, 616843
  • LMPH3
  • Hereditary lymphoedema type III
  • 2nd trimester fetal hydrops, Nuchal translucency likely to be normal, Lethal and non lethal cases within the same family
OMIM
611184
Clinvar variants
Variants in PIEZO1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

21 Dec 2016, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

21 December 2016. External reviews were assessed, and panel was revised according to expert review, internal discussion and additional curation. Following internal discussion, all genes from the V1.14 'RASopathies' panel were added as green EXCLUDING NF1 and SPRED1- a cautious approach was taken because Fetal hydrops is a fetal panel. All relevant genes from the 'Mucopolysaccharideosis, Gaucher, Fabry' V1.0 panel (lysosomal storage disorders) were also added to the Fetal hydrops panel as green together with genes from the literature where there is a reasonable link between the corresponding lysosomal storage disorder (LSD) and Fetal hydrops. All PEX genes from the V1.2 'Peroxisomal disorders' panel were added as green based on a link between peroxisomal biogenesis disorders and Fetal hydrops.

19 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

19 Dec 2016, Gel status: 4

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for PIEZO1 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

19 Dec 2016, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for PIEZO1 were set to Lymphedema, hereditary, III, 616843; LMPH3; Hereditary lymphoedema type III; 2nd trimester fetal hydrops, Nuchal translucency likely to be normal, Lethal and non lethal cases within the same family

15 Dec 2016, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for PIEZO1 were set to 26333996; 26387913

15 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

15 Dec 2016, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for PIEZO1 were set to Lymphedema, hereditary, III, 616843; LMPH3; Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema; Hereditary lymphoedema type III; 2nd trimester fetal hydrops, Nuchal translucency likely to be normal, Lethal and non lethal cases within the same family

15 Dec 2016, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for PIEZO1 were set to Lymphedema, hereditary, III, 616843; LMPH3; Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema; 2nd trimester fetal hydrops, Nuchal translucency likely to be normal, Lethal and non lethal cases within the same family

10 Oct 2016, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

PIEZO1 was created by rfoulger

10 Oct 2016, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

PIEZO1 was added to Fetal hydropspanel. Sources: Other