A large novel beta-thalassemia deletion that removes the entire beta-globin gene has been identified in a Chinese family with elevated fetal hemoglobin levels (Hb F), according to a report published in Hemoglobin. The findings broaden the known mutation spectrum in thalassemia.
Researchers recruited a Chinese family with thalassemia of unclear etiology to participate in a thalassemia screening program. The proband was a 5-year-old girl who was clinically diagnosed with beta-thalassemia major at age 1; she presented with severe anemia, hepatosplenomegaly, jaundice, and elevated Hb F and requires regular blood
transfusion therapy. The team collected blood samples from the proband and her parents for hematological analysis and routine genetic testing.
The researchers confirmed the father as a beta-thalassemia carrier (heterozygous for codons 14/15 [+G]) but were unable to identify a definitive variant in the mother via routine testing. They found the proband was homozygous for codons 14/15 (+G), a finding that appeared to be inconsistent with Mendelian inheritance. They subsequently conducted targeted next-generation sequencing (NGS) and additional genetic testing to identify and validate the novel deletion variant in both the proband and mother.
The novel beta-thalassemia deletion, named the Chongqing deletion, comprised 3488 base pairs and was associated with high Hb F levels in the proband and mother. The researchers discovered that the deletion removed the entire beta-globin gene, resulting in absent beta-globin (β0).
“[R]outine clinical genotyping assays for thalassemia failed to detect this large novel deletion and also led to misdiagnosis in the proband. In this study, we found the new large [β-thalassemia] deletion variant using targeted NGS and characterized it by Sanger sequencing, which helped to clarify the cause of this thalassemia in the family and also indicated that targeted NGS has the potential for finding rare and novel thalassemia mutations,” highlighted the researchers.
Yin ZZ, Yao J, Wei FX, Chen CY, Yan HM, Zhang M. Targeted next-generation sequencing reveals a large novel β-thalassemia deletion that removes the entire HBB gene. Hemoglobin. Published online November 22, 2022. doi:10.1080/03630269.2022.2145964