Fetal anomalies
Gene: PIEZO1
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
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
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
Publications for gene: PIEZO1 were set to 26333996; 23695678
Tag watchlist was removed from gene: PIEZO1.
Mode of inheritance for gene: PIEZO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PIEZO1 were set to 26333996
Gene: piezo1 has been classified as Green List (High Evidence).
Mode of inheritance for gene: PIEZO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Tag watchlist tag was added to gene: PIEZO1.
Source PAGE Additional Gene List was added to PIEZO1. Added phenotypes hydrops fetalis gene 616843 for gene: PIEZO1
gene: PIEZO1 was added gene: PIEZO1 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: PIEZO1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: PIEZO1 were set to 26333996 Phenotypes for gene: PIEZO1 were set to Congenital lymphatic dysplasia with hydrops and/or lymphoedema