Hereditary xerocytosis - spectrum and clinical manifestations of variants in the PIEZO1 gene, including co-occurrence with a novel β-globin mutation

Characterisation of Asp669Tyr Piezo1 cation channel activity in red blood cells: an unexpected phenotype

“…The de novo comparative study, by whole exome sequencing, of the two parents and of the propositus , revealed one in silico predicted deleterious single anomaly: a heterozygous variation of the Piezo‐type mechanosensitive ion channel component 1 ( PIEZO1 ) gene present in exon 16 (NM_001142864.2:c.2005 G>T), leading to the mutation D669Y in the propositus . The same mutation was reported in two reports compiling data on large sets of patients with DHS 6,7 and in a Portuguese patient displaying ‘sporadic’ xerocytosis (ClinVar Accession number: VCV000829815.1); another variant on the same residue (D669H) with haemolytic anaemia has also been reported 8 . To date, these mutations lack functional characterisation.…”

Coinheritance of PIEZO1 variants and multi‐locus red blood cell defects account for the symptomatic phenotype in beta‐thalassemia carriers

“…Currently, the association of BT and PIEZO1 variants has been described only in three cases. [5][6][7] The analysis of the present cohort of patients demonstrated that the clinical phenotype was more severe for BT carriers with DHS or multi-locus inheritance compared to pure BT carriers in terms of Hb levels, splenomegaly, and hemolytic indices (Table S2, Figure 1B).…”

PIEZO1-dependent erythrocyte dehydration as the mechanism for selection of an allele protecting from severe malaria

“…Due to a similarity in the pathophysiology of sickle cells and RBC from HXaffected people with GoF PIEZO1 variants, and because both types of mutations affect RBC morphology, [30][31][32][33] we first explored if normal and P. falciparum infected RBCE756del show any structural abnormalities. As expected, 3 freshly drawn unprocessed blood from E756del carriers had 6-13% distorted RBC (Fig.…”