Abstract: Hereditary spherocytosis (HS) is the most common inherited hemolytic anemia in populations of northern European descent, arising from mutations in genes encoding key erythrocyte membrane proteins, including ANK1, SPTB, SLC4A1, SPTA1 , and EPB42 . These genetic defects disrupt the vertical linkages between the red blood cell (RBC) plasma membrane and its underlying cytoskeleton, reducing RBC deformability and leading to characteristic spherocytosis, premature hemolysis, and accelerated splenic clearance. Inheritance is predominantly autosomal dominant, although autosomal recessive forms occur, particularly involving SPTA1 and EPB42. Clinically, HS manifests with anemia, jaundice, splenomegaly, and complications such as cholelithiasis. This study aimed to identify and characterize pathogenic variants in primary HS genes, establish genotype–phenotype correlations, and enhance diagnostic accuracy to guide personalized management within a defined cohort. Diagnostic advancements, notably the tests of next-generation sequencing and the eosin-5-maleimide binding test, have improved the detection of genetic heterogeneity, yet regional underdiagnosis persists. A comprehensive understanding of the HS genetic spectrum is therefore critical not only for precise diagnosis and optimized patient care but also for informing the development of future gene-targeted therapies, including CRISPR-based approaches. Regional epidemiological investigations, including limited data from Iraq, suggest that HS remains underdiagnosed despite its significant clinical impact. A comprehensive understanding of the HS genetic spectrum is imperative for accurate diagnosis, optimized personalized management, and the eventual development of gene-based therapeutic interventions.
Abdulhassn et al. (Sat,) studied this question.