Abstract
Hereditary xerocytosis (HX) is a rare, autosomal dominant congenital hemolytic anemia (CHA) characterized by erythrocyte dehydration with presentation of various degrees of hemolytic anemia. HX is often misdiagnosed as hereditary spherocytosis or other CHA. Here we report three cases of suspected HX and one case of HX associated with β-thalassemia.Sanger method was used for sequencing cDNA of the PIEZO1 gene. Variants were evaluated for potential pathogenicity by MutationTaster, PROVEAN, PolyPhen-2 and M-CAP software, and by molecular modeling.Four different variants in the PIEZO1 gene were found, including three substitutions (p.D669H, p.D1566G, p.T1732 M) and one deletion (p.745delQ). In addition, in the patient with the p.T1732 M variant we detected a 12-nucleotide deletion in the β-globin gene leading to a deletion of amino acids 62AHGK65. The joint presence of mutations in two different genes connected with erythrocytes markedly aggravated the presentation of the disease. Bioinformatic analysis and molecular modeling strongly indicated likely deleterious effects of all four PIEZO1 variants, but co-segregation analysis showed that the p.D1566G substitution is in fact non-pathogenic.Identification of causative mutations should improve the diagnosis and management of HX and provide a new insight into the molecular basis of this complex red blood cell abnormality.
Highlights
Hereditary xerocytosis (HX), known as dehydrated hereditary stomatocytosis (DHS), is a rare red blood cell membrane disorder resulting in hemolytic anemia with diverse presentation and iron overload
In this patient symptoms of anemia/jaundice have been noted since birth and she was occasionally transfused
Splenectomy should not be performed in the cases of hereditary xerocytosis due to an increased risk of venous thrombosis [19]
Summary
Hereditary xerocytosis (HX), known as dehydrated hereditary stomatocytosis (DHS), is a rare red blood cell membrane disorder resulting in hemolytic anemia with diverse presentation and iron overload. Inherited missense mutations in the PIEZO1 gene encoding a large mechanosensitive ion channel, affecting mainly its highly conserved COOH-terminus, have been identified in HX patients [1]. They increase the cation permeability of the membrane, which leads to erythrocyte dehydration. The clinical presentation of hereditary xerocytosis is markedly heterogeneous, ranging from normal hemoglobin values to severe anemia, with borderline macrocytosis, increased cell hemoglobin content (MCH) and increased mean corpuscular hemoglobin concentration (MCHC) [5] Another type of RBC disorder with well-understood genetic and molecular etiology is βthalassemia. Co-segregation studies were used to verify the predicted pathogenicity of two of the novel variants
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
