Anemia affects 1.6 billion of people worldwide, about 10% of these individuals are affected by rare anemias of which 80% are hereditary.1 Hereditary anemias (HA) embrace a highly heterogeneous group of disorders characterized by anemia of variable degree and by complex genotype-phenotype correlations. Differential diagnosis, classification, and patient stratification among HA are often very difficult.
To date, the major current application of next generation sequencing (NGS) in diagnostics is through disease-targeted tests for which multiple causal genes are known. Some studies have already demonstrated the utility of targeted-NGS (t-NGS) approach in the study of specific subtypes of HA patients. Here, we described the diagnostic workflow based on t-NGS that we developed for the diagnosis of patients affected by HA. Within this wide group of disorders, we included: (1) hyporegenerative anemias, as congenital dyserythropoietic anemias (CDA); (2) hemolytic anemias due to red cell membrane defects, as hereditary spherocytosis (HS) and stomatocytosis (HSt); hemolytic anemias due to enzymatic defects, as pyruvate kinase (PK) deficiency.1–5
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2. Gambale A et al. Diagnosis and management of congenital dyserythropoietic anemias. Expert Rev Hematol. 2016;9(3):283-96.
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Andolfo I et al. New insights on hereditary erythrocyte membrane defects. Haematologica. 2016;101(11):1284–1294.
4. Andolfo I et al. Hereditary stomatocytosis: An underdiagnosed condition. Am J Hematol. 2018;93(1):107–121.
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Canu G et al. Red blood cell PK deficiency: An update of PK-LR gene mutation database. Blood Cells Mol Dis. 2016;57:100–109.
