The Effect of HBB: c.-121C>T Variant [–71 (C>T)] on the β-Globin Promoter: Case Series Study

Abstract

One of the effective strategies in controlling thalassemia is recognition of carriers, followed by prenatal diagnosis (PND) to prevent the occurrence of new cases. There are some rare mutations and variants, for which there are not enough evidences of their effects, and can lead to misdiagnosis and even cause confusion in decision about termination of pregnancy. That is why it is very critical to know the effect of each mutation on the β chain gene. The variant of HBB: c.-121C>T [–71 (C>T)] located in the CAAT box of the promoter region, is a rare mutation. We report seven patients in Hormozagn Province, Iran, who were referred to the PND Center of Hormozgan University of Medical Science (HUMS), Bandar Abbas, Iran during 10 years (2010–2020). Briefly, this mutation causes minor changes in blood indices [mean corpuscular volume (MCV): 75.0 ± 4.0 fL; mean corpuscular hemoglobin (MCH): 25.8 ± 2.5 pg; Hb A2: 3.4 ± 0.5%] showed anemia with a trait milder than minor β-thalassemia (β-thal). Though the existence of α mutations (deletions/point mutations) along with HBB: c.-121C>T can change blood indices due to the changes in α/β ratio. The phenotype of β-thal intermedia (β-TI) was observed in one case, who was a compound heterozygosity for codon 15 (G>A)/–71(C>T) (HBB: c.48G>A/HBB: c.-121C>T. The analysis of transcription level by real-time polymerase chain reaction (real-time PCR) confirmed that this allele induces a mild β+ phenotype due to a decrease in the transcription level.