Characterization of a novel 8.2 kb deletion causing beta-thalassemia

•Routine thalassemia test failed to explain clinical manifestation of the proband.•MLPA and NGS facilitate the identification of disease-causing mutations.•A novel 8.2 kb deletion causing beta-thalassemia inherited over three generations was characterized. Thalassemia is a prevalent monogenic blood disorder, clinically classified into alpha- and beta-thalassemia, characterized by the imbalance of the alpha- and beta-globin chains that constitute adult hemoglobin. Copy number variations (CNVs) and single nucleotide variants in globin genes are the primary genetic defects causing thalassemia. During a prenatal examination, a pregnant woman was suspected to be a carrier of thalassemia, exhibiting microcytic hypochromic anemia and abnormal hemoglobin constituents. Gap-polymerase chain reaction (Gap-PCR) and reverse dot blot (PCR-RDB) techniques did not detect any common thalassemia mutations. We conducted hematological examination and further genetic analyses on the proband’s family with three generations. Multiplex ligation-dependent probe amplification (MLPA) was employed to identify CNVs, targeted next-generation sequencing was used to screen for potential pathogenic variants, which were subsequently validated by Sanger sequencing. The hematological parameters of the proband, her father and her son all indicated they were beta-thalassemia carriers. MLPA results revealed a large deletion in beta-globin cluster. Further investigation confirmed the presence of a novel 8.2 kb deletion (NC_000011.10:g.5224208_5232469del) in the proband, her father, and her son, specifically covering the entire HBB gene while not impacting other globin genes. We found a novel 8.2 kb deletion leading to beta-thalassemia in a Chinese family in which three generations had been affected. This novel deletion may broaden the spectrum of known mutations in thalassemia and provide a reference for clinically suspected cases.