A Novel Mutation in the Promoter Region of the -Globin Gene: HBB: c.-127G > C

Abstract

Novel -globin gene mutations are still occasionally being reported, especially when evaluating milder phenotypes. We report here a novel putative mutation in the promoter region of the -globin gene and assess its clinical implications. A family, parents and four siblings, with hematological and clinical features suspected of being -globin gene mutation(s), were involved in this study. In addition to hematological and clinical evaluations of the whole family, molecular analyses of the -globin gene were performed by direct sequencing. Sequencing of the -globin gene revealed a novel genomic alteration in the regulatory region of the gene. This novel genomic alteration was defined as HBB: c.-127G>C according to the Human Genome Variation Society (HGVS) nomenclature. Two siblings were found to be carriers of the HBB: c.-127G>C mutation, while the other two siblings were carriers of the codon 8 (-AA) (HBB: c.25_26delAA) deletion of the -globin gene. The mother was a compound heterozygote for the codon 8 and HBB: c.-127G>C mutations. Based on hematological and clinical evaluations, we conclude that this novel -globin gene promoter region change would be associated with a mild phenotype of -thalassemia (-thal).