Comprehensive genomic analysis identifies a diverse landscape of sideroblastic and non-sideroblastic iron related anemias with novel and pathogenic variants in an iron deficient endemic setting

Inherited iron metabolism defects are possibly missed or underdiagnosed in iron-deficient endemic settings due to a lack of awareness or a methodical screening approach. Hence, we planned a systematic evaluation of anemia cases (2019-2021) based on clinical phenotype, normal screening tests (HPLC, alpha gene sequencing, ESR, CRP, tTG), and abnormal iron profile by targeted NGS (26 gene-panel) supplemented with whole exome, MLPA/mtDNA sequencing and CMA. Novel variants in ALAS2, STEAP3, and HSPA9 genes were functionally validated.