A novel fusion gene and a common α0-thalassemia deletion cause hemoglobin H disease in a Chinese family

Genetic recombination has been implicated as a mechanism that drives mutagenesis in the human globin gene clusters, either as a result of unequal crossover or gene conversion. In this paper, a novel fusion gene was identified in a Chinese girl with hemoglobin H disease. The proband's father was a compound heterozygote for the common − α4.2 deletion and this fusion gene, and her mother was heterozygous for the common −−SEA deletion (−−SEA/αα). Both her parents had a hypochromic and microcytic red cell phenotype and a normal hemoglobin level. Molecular studies revealed a compound heterozygote for the −−SEA deletion and this novel fusion gene and the patient had the clinical features of classic hemoglobin H disease. Sequence analysis revealed that the mutant gene was the result of a fusion between the α2 and ψα1 genes. The recombination began at exon 3 of α2 gene, crossing with exon 3 of the ψα1 gene. With this recombination, the conservative 3′UTR of the α2 gene was changed, and an extensive transcript with a new signal 1048 bp 3′ to the terminating codon was found. The abnormal transcripts of the fusion gene read through the intergenic sequence.