Hereditary Erythrocytosis
Gene: PIEZO1
After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.
GMS reviewers note that it is a very polymorphic gene that will impose a substantial analysis burden. Publication identifies 4 "possibly" causative mutations and stresses the importance of electrophysiological assessment of variants, which is not always easy to arrange.Created: 1 Feb 2023, 8:29 a.m. | Last Modified: 1 Feb 2023, 8:34 a.m.
Panel Version: 1.46
Comment on list classification: New association with this phenotype identified by external reviewer, Dmitrijs Rots. Rating Amber but there is sufficient evidence to promote this gene to Green at the next GMS panel update.Created: 4 Jan 2022, 2:05 p.m. | Last Modified: 4 Jan 2022, 2:05 p.m.
Panel Version: 1.44
Well-established association of PIEZO1 variants with hereditary xerocytosis (MIM# 194380) which typically is accompanied by haemolytic anaemia. However, a small group of patients have been found with absent or well-compensated haemolysis but instead with erythrocytosis (PMID: 33181827, 31298594, 30655378).
Inclusion on this panel discussed with Helen Brittain (Genomics England Clinical Team) who states: "The mechanism is not exactly clear, in particular as to why some present with the xerocytosis where as others have erythrocytosis / mild haemolytic jaundice. It does appear there are sufficient cases with a phenotype that is relevant for this panel and I can see a number of different missense variants reported. On that basis it would meet the criteria for green rating. Suspected GOF."Created: 4 Jan 2022, 2:03 p.m. | Last Modified: 4 Jan 2022, 2:03 p.m.
Panel Version: 1.43
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications
Pathogenic variants (gain-of-function missense) in the PIEZO1 has been previously identified as a cause of hereditary xerocytosis. Recently, it has been Identified that similar (likely) pathogenic GoF missense variants likely causes erythrocytosis in 5 individuals. Functional analysis confirms pathogenicity of the variants. Patients also displayed features of hereditary xerocytosis.
Sources: LiteratureCreated: 30 Nov 2021, 9:26 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Erythrocytosis
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
Tag Q1_22_rating was removed from gene: PIEZO1.
Gene: piezo1 has been classified as Amber List (Moderate Evidence).
Tag Q1_22_rating tag was added to gene: PIEZO1.
Publications for gene: PIEZO1 were set to PMID: 33181827
Phenotypes for gene: PIEZO1 were changed from Erythrocytosis to Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, OMIM:194380; Erythrocytosis
gene: PIEZO1 was added gene: PIEZO1 was added to Hereditary Erythrocytosis. Sources: Literature Mode of inheritance for gene: PIEZO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PIEZO1 were set to PMID: 33181827 Phenotypes for gene: PIEZO1 were set to Erythrocytosis Penetrance for gene: PIEZO1 were set to unknown Mode of pathogenicity for gene: PIEZO1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: PIEZO1 was set to GREEN