In this context, targeted sequencing analysis using NGS appears as an advantageous tool since it enables simultaneous testing of several genes and has proven useful for accurate, rapid, and cost-effective diagnosis of several diseases, including hereditary anemias. Molecular diagnosis using routine sequencing approaches is impractical due to the large number and size of involved genes. Thus, the genetic analysis would provide more informative clues for differential diagnosis, patient stratification, and genetic counseling. Traditional laboratory workflow for HA diagnosis encompasses several lines of tests, adding cost and delay to the results. Clinicians rely on morphologic/biochemical tests and clinical characteristics however, these approaches fail to detect a percentage of the cases, and classification through these methods is not accurate.
Genetic defects occurring in HA arise from a variety of different mutations that affect production of red blood cells in the bone marrow or cause red cell destruction due to defects in structural proteins of the cell, synthesis of the globin chains, or the expression of intracellular enzymes. Hereditary anemias (HA) are a genetically and phenotypically diverse group of disorders associated with mutations in more than 70 genes. This is the first comprehensive genetic analysis for hereditary anemias in the Brazilian population, contributing to a better understanding of the genetic basis and phenotypic consequences of these rare conditions in our population. We also identified two cases with dominant HS presenting null mutations in trans with α- LELY in SPTA1 gene. Remarkably, mutations in the SPTB gene (β-spectrin ) were found in 34.6% of the patients with hereditary spherocytosis (HS), suggesting that SPTB is a major HS gene in the Southeast of Brazil. We analyzed 36 patients, and potentially pathogenic variants were identified in 26 cases (72%). To overcome this problem, we customized a targeted sequencing panel covering 35 genes previously associated to red cell disorders. A conventional gene-by-gene sequencing approach is expensive and highly time-consuming, due to the genetic complexity of these diseases. The genetic screening of the main genes is important for timely diagnosis, since routine laboratory tests fail in a percentage of the cases, appropriate treatment decisions, and genetic counseling purposes. Causative mutations occur in a wide range of genes leading to deficiencies in red cell production, structure, or function. Hereditary anemias are a group of heterogeneous disorders including hemolytic anemias and hyporegenerative anemias, as congenital dyserythropoietic anemia (CDA).
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