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Updated: Sep 9, 2025

A Precision Medicine Tool for Measurement and Monitoring of Hemoglobin S in Sickle Cell Disease Patients Receiving Transfusion Therapy
Severe Hemolytic Phenotype in Children With Sickle Cell Anemia and Co-Inherited Red Blood Cell Variants
Meghana Srinivas1, Sue Jaspersen2, David B Wilson2
1Department of Pediatrics, East Tennessee State University School of Medicine, Johnson City, Tennessee, USA.
Abstract:
Remarkable phenotypic variability exists among individuals with sickle cell anemia (SCA), which may be explained by co-inheritance of traits affecting red blood cell (RBC) biology, such as genes affecting globin expression or glucose-6-phosphate dehydrogenase enzyme activity. Here, we describe three children with severe SCA who have co-inherited variants in genes for membrane proteins (SPTA1 and EPB1) and PIEZO1. These cases suggest that variants in RBC membrane proteins may contribute to SCA severity and phenotypic variation. Co-Inheritance of such variants could, in theory, affect outcomes of emerging SCA therapies, including genetic modification treatments.
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