Identification of a novel frameshift mutation at codon 53 (-T) in the beta-globin gene causing dominantly inherited beta-thalassemia in a Chinese Miao family

Abstract

beta-thalassemia, one of the most common inherited disorders of hemoglobin synthesis in the world, is genetically heterogeneous with over 200 different beta-globin mutations worldwide. In this study, we describe a novel frameshift beta-thalassemia mutation at codon (cd) 53 (-T) in exon 2 of the beta-globin gene in a Chinese Miao family. In this family, all seven heterozygotes with this mutation presented with moderate anemia, jaundice, splenomegaly and elevated hemoglobin A2 levels. None of them had been transfused or carried any other known alpha/beta-globin mutation. Pedigree analysis indicated an autosomal dominant inheritance pattern in this family. Two new haplotypes "----+-+" and "--+++-+" were identified by restriction fragment length polymorphism (RFLP) haplotype analysis. The former was associated with the cd53 (-T) mutation and the latter only existed in one family member. Thus, a novel frameshift cd53 (-T) mutation may lead to mild thalassemia intermedia even though there is no statistically significant difference in beta-globin messenger RNA (mRNA) level between six heterozygotes and six normal subjects.