International Journal of Hematology

DOI: 10.1007/s12185-019-02716-9 Pages: 618-626

Study of pathophysiology and molecular characterization of congenital anemia in India using targeted next-generation sequencing approach

1. ICMR-National Institute of Immunohematology, Department of Hematogenetics

2. Tohoku University Graduate School of Medicine, Department of Hematology and Rheumatology

3. Hirosaki University Graduate School of Medicine, Department of Pediatrics

4. Nagoya University Graduate School of Medicine, Department of Pediatrics

Correspondence to:
Prabhakar S. Kedar
Tel: + 9122 24138518



Most patients with anemia are diagnosed through clinical phenotype and basic laboratory testing. Nonetheless, in cases of rare congenital anemias, some patients remain undiagnosed despite undergoing an exhaustive workup. Genetic testing is complicated by the large number of genes that are involved in rare anemias, due to similarities in the clinical presentation. We sought to enhance the diagnosis of patients with congenital anemias by using targeted next-generation sequencing. The genetic diagnosis was performed by gene capture followed by next-generation sequencing of 76 genes known to cause anemia syndromes. Genetic diagnosis was achieved in 17 of 21 transfusion-dependent patients and undiagnosed by conventional workup. Four cases were diagnosed with red cell membrane protein defects, four patients were diagnosed with pyruvate kinase deficiency, one case of adenylate kinase deficiency, one case of glucose phosphate isomerase deficiency, one case of hereditary xerocytosis, three cases having combined membrane and enzyme defect, two cases with Diamond–Blackfan anemia (DBA) and 1 with CDA type II with 26 different mutations, of which 21 are novel. Earlier incorporation of this NGS method into the workup of patients with congenital anemia may improve patient care and enable genetic counselling.

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