Double heterozygosity for the codon beta 39 C-to-T nonsense mutation and atriplicate alpha-globin gene locus can cause "dominantly" inherited beta-thalassemia intermedia

Background: A beta-thalassemia intermedia phenotype can be caused by multip le genotypes. Methods: We studied a family where the mother was hematologically normal an d both father and daughter had B-thalassemia intermedia. Results: Both affected individuals were heterozygous for a codon 39 CAG-to- TAG mutation, They also were heterozygous for a triplicate alpha-globin gen e locus (alpha alpha alpha(anti 3.7)). Conclusions: This compound heterozygous condition of a beta(39) C-to-T muta tion and triplicate alpha-globin gene increases alpha:beta-globin chain imb alance and accounts for the presence of beta-thalassemia intermedia. The pr oband received both an abnormal beta-globin gene and a triplicate alpha-glo bin locus from her father. Although the phenotype seems to be dominantly in herited, because of independent segregation of the alpha- and beta-globin g enes, it is more accurately an example of polygenic inheritance.